Trial Outcomes & Findings for A Challenge Study to Assess the Safety, Immunogenicity and Efficacy of a Malaria Vaccine Candidate (NCT NCT02927145)

NCT ID: NCT02927145

Last Updated: 2022-02-18

Results Overview

PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint for the Phase IIa stage of the trial, and comparison of the endpoint between the Groups 5 and 6 will constitute the primary analysis for efficacy.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 88 participants
• Primary outcome timeframe: Measured during CHMI
• Results posted on: 2022-02-18

Participant Flow

Group 5 and 6 volunteers were invited to join the re-challenge study and formed Groups 7 and 8

Participant milestones

Measure	Group 1-Phase Ia The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
Initial Recruitment STARTED	12	12	12	14	17	15	0	0	6
Initial Recruitment COMPLETED	12	11	11	10	14	14	0	0	4
Initial Recruitment NOT COMPLETED	0	1	1	4	3	1	0	0	2
Invitation for Additional Challenge STARTED	0	0	0	0	0	0	9	8	0
Invitation for Additional Challenge COMPLETED	0	0	0	0	0	0	8	8	0
Invitation for Additional Challenge NOT COMPLETED	0	0	0	0	0	0	1	0	0

Reasons for withdrawal

Measure	Group 1-Phase Ia The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
Initial Recruitment Withdrawal by Subject	0	1	1	4	1	1	0	0	2
Initial Recruitment Adverse Event	0	0	0	0	2	0	0	0	0
Invitation for Additional Challenge Pregnancy	0	0	0	0	0	0	1	0	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Group 1 n=12 Participants The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults.	Group 2 n=12 Participants The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3 n=12 Participants Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4 n=14 Participants Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5 n=17 Participants The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity. Note, group 7 constitutes volunteers from groups 5 so is not presented separately	Group 6 n=15 Participants Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations. Note, group 8 constitutes volunteers from groups 6 so is not presented separately	Group 9 n=6 Participants Group 9 are new infectivity controls	Total n=88 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=17 Participants	0 Participants n=15 Participants	0 Participants n=6 Participants	0 Participants n=88 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=12 Participants	12 Participants n=12 Participants	12 Participants n=12 Participants	14 Participants n=14 Participants	17 Participants n=17 Participants	15 Participants n=15 Participants	6 Participants n=6 Participants	88 Participants n=88 Participants
Age, Categorical >=65 years	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=17 Participants	0 Participants n=15 Participants	0 Participants n=6 Participants	0 Participants n=88 Participants
Age, Continuous	32 Years n=12 Participants	28 Years n=12 Participants	29 Years n=12 Participants	31 Years n=14 Participants	27 Years n=17 Participants	27 Years n=15 Participants	24 Years n=6 Participants	29 Years n=88 Participants
Sex: Female, Male Female	9 Participants n=12 Participants	7 Participants n=12 Participants	8 Participants n=12 Participants	9 Participants n=14 Participants	12 Participants n=17 Participants	6 Participants n=15 Participants	4 Participants n=6 Participants	55 Participants n=88 Participants
Sex: Female, Male Male	3 Participants n=12 Participants	5 Participants n=12 Participants	4 Participants n=12 Participants	5 Participants n=14 Participants	5 Participants n=17 Participants	9 Participants n=15 Participants	2 Participants n=6 Participants	33 Participants n=88 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Measured during CHMI

Population: Group 5 vs Group 6 and Group 7 vs Group 9 compared as vaccinees versus primary infectivity controls

PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint for the Phase IIa stage of the trial, and comparison of the endpoint between the Groups 5 and 6 will constitute the primary analysis for efficacy.

Outcome measures

Measure	Group 1-Phase Ia The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa n=14 Participants The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa n=14 Participants Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa n=8 Participants Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa n=4 Participants Group 9 are new infectivity controls
Efficacy of the RH5.1/AS01 Vaccine by Demonstrating a Reduced PMR in Vaccinated Subjects Compared to Infectivity Controls Against 3D7 Clone Parasites in a CHMI Model.	—	—	—	—	8.12 Parisite multiplication rate (PMR) Standard Deviation 1.13	9.75 Parisite multiplication rate (PMR) Standard Deviation 2.46	7.62 Parisite multiplication rate (PMR) Standard Deviation 1.44	—	11.22 Parisite multiplication rate (PMR) Standard Deviation 1.92

PRIMARY outcome

Timeframe: 8 months

Population: Note, detailed adverse event data is outlined within the study publication. Groups 6, 8 and 9 were not assessed for adverse events as part of this objective as they did not receive the trial vaccine. This objective is assessing the safety of the vaccine itself and therefore is not applicable to these groups.

Solicited and unsolicited adverse events collected passively and actively for 28 days post each vaccination.

Number of volunteers reporting any unsolicited AEs post-any vaccination, as reported to investigators or in electronic diaries.

Outcome measures

Measure	Group 1-Phase Ia n=12 Participants The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia n=12 Participants The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia n=12 Participants Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia n=14 Participants Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa n=17 Participants The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa n=9 Participants Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
Safety of RH5.1/AS01 in Healthy Malaria-naïve Adults in the UK.	9 Participants	11 Participants	9 Participants	10 Participants	14 Participants	3 Participants	—	—	—

PRIMARY outcome

Timeframe: 2 weeks post final vaccination

Population: GIA activity of 10mg/ml purified IgG was measured at 2 weeks following final vaccination (D70 for Groups 1, 2 \& 4 and D196 for Group 3). Objective is not applicable for groups 5-9.

The specific endpoints for GIA in vitro will be assessed from a titration of the purified IgG in the assay.

Outcome measures

Measure	Group 1-Phase Ia n=12 Participants The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia n=11 Participants The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia n=11 Participants Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia n=10 Participants Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
the in Vitro Growth Inhibition Activity (GIA) Against 3D7 Clone P. Falciparum Parasites of IgG Purified From the Serum of Vaccinees.	75.2 percentage of growth inhibition Standard Deviation 20.25	69.9 percentage of growth inhibition Standard Deviation 11.65	71.3 percentage of growth inhibition Standard Deviation 13.76	71.6 percentage of growth inhibition Standard Deviation 13.18	—	—	—	—	—

SECONDARY outcome

Timeframe: 2 weeks post final vaccination

Population: Anti-RH5\_FL IgG (ug/mL) at 2 weeks post final vaccination in groups 1-4, Fig 1C. This objective is not applicable to groups 5-9

Antibody responses to the RH5.1 protein generated by vaccination

Outcome measures

Measure	Group 1-Phase Ia n=12 Participants The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia n=11 Participants The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia n=11 Participants Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia n=10 Participants Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
the Humoral Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens.	86.9 ug/mL Standard Deviation 51.75	88.1 ug/mL Standard Deviation 40.11	124.4 ug/mL Standard Deviation 81.62	95.6 ug/mL Standard Deviation 56.07	—	—	—	—	—

SECONDARY outcome

Timeframe: 2 weeks post final vaccination

Population: RH5-specific T cell responses were assessed by ex-vivo IFN-γ ELISPOT in fresh PBMC following stimulation with either RH5.1 protein at 2 weeks post final vaccination in Groups 1-4. This objective is not applicable to groups 5-9.

T cell responses to the RH5.1 protein generated by vaccination

Outcome measures

Measure	Group 1-Phase Ia n=12 Participants The study is designed to assess a 'standard' protein-in-adjuvant vaccination regimen- 2µg RH5.1/ 0.5mL AS01- of 3 doses given four weeks apart, with dose escalation to assess the best dose in healthy adults. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 2- Phase Ia n=11 Participants The dose used will be- 10µg RH5.1/ 0.5mL AS01. The total number of volunteers recruited to Groups 1 and 2 will be decided based on the immunogenicity of the vaccines at the 2 µg and 10 µg doses. If the doses are immunogenic the groups (1 and 2) will be recruited to a total of 12 volunteers. RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 3-Phase Ia n=11 Participants Group 3 will receive 50µg RH5.1/ 0.5mL AS0 The ultimate aim is to assess the safety and immunogenicity of giving the 'standard' first two doses of the vaccine followed by a delayed fractional dose (10 µg). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 4-Phase Ia n=10 Participants Group 3 and 4 will be recruited simultaneously. The dose of vaccine for this group is same as that of 3 (50µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 5-Phase IIa The vaccination dose for Group 5 was decided following the analysis of safety and exploratory immunology assays from Groups 1, 2 and 4. The dose of vaccine for this group is the same as that of group 2 (10µg RH5.1/ 0.5mL AS01). RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 6-Phase IIa Group 6 volunteers will be infectivity controls, so will not receive any vaccinations. Groups 5 and 6 will only be recruited once at least 6 volunteers in Group 4 have completed all vaccinations.	Group 7-Phase IIa Group 7 are Group 5 volunteers who will receive a fourth dose of IMP (10µg RH5.1/ 0.5mL AS01) RH5.1/ ASO1: The RH5.1 protein consists of the entire full-length ectodomain of the PfRH5 antigen (amino acids E26 - Q526) with the sequence based on the 3D7 clone of P. falciparum. The AS01 adjuvant system has been developed and manufactured by GlaxoSmithKline (GSK) Biologicals and is presented as a liquid solution in a monodose glass vial. AS01 is a liposome-based Adjuvant System with a specific aim to improve cell-mediated immunity.	Group 8 -Phase IIa Group 8 are infectivity controls who were originally in Group 6.	Group 9 -Phase IIa Group 9 are new infectivity controls
the Cellular Immunogenicity of RH5.1/AS01 Using Different Vaccine Doses and Vaccination Regimens.	570 SFU per million PBMC Standard Deviation 439.4	140.7 SFU per million PBMC Standard Deviation 343.9	277.3 SFU per million PBMC Standard Deviation 328.4	713.3 SFU per million PBMC Standard Deviation 396.4	—	—	—	—	—

SECONDARY outcome

Timeframe: 8 months

Statistical correlation between anti-RH5 antibody responses induced by the RH5.1 vaccine and PMR.

A non-linear regression curve for all samples combined is available in the trial manuscript ; data is not presented here.

Outcome measures

Outcome data not reported

Adverse Events

Group 1

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Group 2

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Group 3

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Group 4

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Group 5

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Group 6

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 7

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Group 8

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 9

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Group 1 n=12 participants at risk 3 doses of 2µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 2 n=12 participants at risk 3 doses of 10µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 3 n=12 participants at risk 2 doses of 50µg RH5.1 in 0.5mL AS01 at days 0 and 28, followed by 10µg RH5.1 in 0.5mL AS01 at day 182	Group 4 n=14 participants at risk 3 doses of 50µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 5 n=17 participants at risk 3 doses of 10 µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 6 n=15 participants at risk Primary CHMI controls	Group 7 n=9 participants at risk Group 5 participants receiving 1 further dose of 10 µg RH5.1 in 0.5 mL AS01 approximately 4 months after the last immunisation	Group 8 n=8 participants at risk Secondary CHMI controls	Group 9 n=6 participants at risk Primary CHMI controls
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/17 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
Surgical and medical procedures Tonsilectomy	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	5.9% 1/17 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/17 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	11.1% 1/9 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.

Other adverse events

Measure	Group 1 n=12 participants at risk 3 doses of 2µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 2 n=12 participants at risk 3 doses of 10µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 3 n=12 participants at risk 2 doses of 50µg RH5.1 in 0.5mL AS01 at days 0 and 28, followed by 10µg RH5.1 in 0.5mL AS01 at day 182	Group 4 n=14 participants at risk 3 doses of 50µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 5 n=17 participants at risk 3 doses of 10 µg RH5.1 in 0.5mL AS01 at days 0, 28 and 56	Group 6 n=15 participants at risk Primary CHMI controls	Group 7 n=9 participants at risk Group 5 participants receiving 1 further dose of 10 µg RH5.1 in 0.5 mL AS01 approximately 4 months after the last immunisation	Group 8 n=8 participants at risk Secondary CHMI controls	Group 9 n=6 participants at risk Primary CHMI controls
Musculoskeletal and connective tissue disorders Back Pain	25.0% 3/12 • Number of events 5 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/17 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	11.1% 1/9 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Headache	16.7% 2/12 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	25.0% 3/12 • Number of events 8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	16.7% 2/12 • Number of events 7 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	14.3% 2/14 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	17.6% 3/17 • Number of events 6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	50.0% 6/12 • Number of events 9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	14.3% 2/14 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	17.6% 3/17 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Oropharyngeal pain	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	25.0% 3/12 • Number of events 6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	14.3% 2/14 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	23.5% 4/17 • Number of events 5 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	11.1% 1/9 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Rhinitis	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	16.7% 2/12 • Number of events 4 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	25.0% 3/12 • Number of events 4 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	14.3% 2/14 • Number of events 4 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	23.5% 4/17 • Number of events 4 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Rhinorrhoea	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	25.0% 3/12 • Number of events 6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	5.9% 1/17 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
Gastrointestinal disorders Nausea	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	16.7% 2/12 • Number of events 4 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	16.7% 2/12 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	5.9% 1/17 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Local Reaction	16.7% 2/12 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	16.7% 2/12 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	21.4% 3/14 • Number of events 6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	5.9% 1/17 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
General disorders Insomnia	16.7% 2/12 • Number of events 3 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	8.3% 1/12 • Number of events 2 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	7.1% 1/14 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/17 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/9 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.
Musculoskeletal and connective tissue disorders Athralgia	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/12 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/14 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/17 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/15 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	11.1% 1/9 • Number of events 1 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/8 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.	0.00% 0/6 • Data on solicted adverse events were collected for 7 days after vaccinated and unsolicited adverse events for 28 days post-vaccination. Data on serious adverse events and adverse events of special interest were collected for the study duration. Study duration was 240 days post first vaccination in groups 1, 2 and 4, 366 days post first vaccination in group 3 and 90 days post challenge in groups 5 and 7 Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever. Note: mortality \& serious adverse events reported for all study groups, non-serious adverse events reported relate to vaccinations only.

Additional Information

Dr Angela Minassian

University of Oxford

Phone: 0044 01865611425

Email: angela.minassian@ndm.ox.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place