Trial Outcomes & Findings for COVID-19 Booster Study in Healthy Adults in Australia (NCT NCT05658523)

Last Updated: 2026-01-02

Results Overview

Serum samples collected at 28-days post booster vaccination from the two intervention groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

496 participants

Primary outcome timeframe

28-days post booster vaccination

Results posted on

2026-01-02

Participant Flow

Participant milestones

Participant milestones
Measure	Bivalent Moderna (mRNA-1273.214) Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Baseline STARTED	177	176	143
Baseline COMPLETED	176	176	143
Baseline NOT COMPLETED	1	0	0
28 Days STARTED	177	176	143
28 Days COMPLETED	175	171	143
28 Days NOT COMPLETED	2	5	0
6 Months STARTED	175	175	143
6 Months COMPLETED	168	158	136
6 Months NOT COMPLETED	7	17	7
12 Months STARTED	173	165	137
12 Months COMPLETED	163	147	124
12 Months NOT COMPLETED	10	18	13
18 Months STARTED	167	155	132
18 Months COMPLETED	133	124	108
18 Months NOT COMPLETED	34	31	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Bivalent Moderna (mRNA-1273.214) Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Baseline No blood draw	1	0	0
28 Days Lost to Follow-up	1	0	0
28 Days Withdrawal by Subject	1	1	0
28 Days Visit missed	0	4	0
6 Months Lost to Follow-up	1	7	2
6 Months Withdrawal by Subject	1	3	4
6 Months Visit missed	5	7	0
6 Months No blood draw	0	0	1
12 Months Lost to Follow-up	2	6	3
12 Months Withdrawal by Subject	4	4	2
12 Months Visit missed	4	8	8
18 Months Lost to Follow-up	5	8	2
18 Months Withdrawal by Subject	17	9	16
18 Months Visit missed	12	14	6

Baseline Characteristics

One participant is missing a weight measurement, as they declined the assessment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.	Total n=496 Participants Total of all reporting groups
Age, Continuous	30 years n=177 Participants	31 years n=176 Participants	39 years n=143 Participants	32 years n=496 Participants
Age, Customized ≥18 to <50 years	150 Participants n=177 Participants	150 Participants n=176 Participants	101 Participants n=143 Participants	401 Participants n=496 Participants
Age, Customized ≥50 years	27 Participants n=177 Participants	26 Participants n=176 Participants	42 Participants n=143 Participants	95 Participants n=496 Participants
Sex: Female, Male Female	116 Participants n=177 Participants	128 Participants n=176 Participants	114 Participants n=143 Participants	358 Participants n=496 Participants
Sex: Female, Male Male	61 Participants n=177 Participants	48 Participants n=176 Participants	29 Participants n=143 Participants	138 Participants n=496 Participants
Region of Enrollment Australia	177 Participants n=177 Participants	176 Participants n=176 Participants	143 Participants n=143 Participants	496 Participants n=496 Participants
BMI	24.7 kg/m^2 n=176 Participants • One participant is missing a weight measurement, as they declined the assessment.	24.8 kg/m^2 n=176 Participants • One participant is missing a weight measurement, as they declined the assessment.	24.2 kg/m^2 n=143 Participants • One participant is missing a weight measurement, as they declined the assessment.	24.5 kg/m^2 n=495 Participants • One participant is missing a weight measurement, as they declined the assessment.
Number of times tested positive for SARS-CoV-2 0 prior positive SARS-CoV-2 tests	37 Participants n=177 Participants	30 Participants n=176 Participants	42 Participants n=143 Participants	109 Participants n=496 Participants
Number of times tested positive for SARS-CoV-2 1 prior positive SARS-CoV-2 tests	109 Participants n=177 Participants	113 Participants n=176 Participants	69 Participants n=143 Participants	291 Participants n=496 Participants
Number of times tested positive for SARS-CoV-2 2 prior positive SARS-CoV-2 tests	26 Participants n=177 Participants	28 Participants n=176 Participants	28 Participants n=143 Participants	82 Participants n=496 Participants
Number of times tested positive for SARS-CoV-2 3 prior positive SARS-CoV-2 tests	5 Participants n=177 Participants	4 Participants n=176 Participants	4 Participants n=143 Participants	13 Participants n=496 Participants
Number of times tested positive for SARS-CoV-2 4 prior positive SARS-CoV-2 tests	0 Participants n=177 Participants	1 Participants n=176 Participants	0 Participants n=143 Participants	1 Participants n=496 Participants
Comorbidities Diabetes mellitus	4 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	4 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	3 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	11 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Gestational diabetes	0 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Obesity (BMI ≥30 kg/m^2)	27 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	33 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	21 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	81 Participants n=495 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Cardiovascular disease	1 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	3 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	5 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Hypertension	8 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	9 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	8 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	25 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Cancer	2 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Chronic obstructive pulmonary disease	0 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Chronic kidney disease	1 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Chronic liver disease	1 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	3 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities History of anaphylaxis	3 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	7 Participants n=495 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Neurological disease	1 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	4 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities On anticoagulant therapy	2 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	2 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	4 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	8 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Cigarette user	5 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	7 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	12 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Pregnant at time of enrolment	1 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	1 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	3 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities Asthma	25 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	28 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	19 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	72 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Comorbidities History of mastocytosis	0 Participants n=177 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=176 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=143 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis	0 Participants n=496 Participants • One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m\^2) and for history of anaphylaxis
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=177 Participants	0 Participants n=176 Participants	1 Participants n=143 Participants	3 Participants n=496 Participants
Race (NIH/OMB) Asian	41 Participants n=177 Participants	33 Participants n=176 Participants	58 Participants n=143 Participants	132 Participants n=496 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=177 Participants	0 Participants n=176 Participants	0 Participants n=143 Participants	0 Participants n=496 Participants
Race (NIH/OMB) Black or African American	0 Participants n=177 Participants	2 Participants n=176 Participants	0 Participants n=143 Participants	2 Participants n=496 Participants
Race (NIH/OMB) White	129 Participants n=177 Participants	139 Participants n=176 Participants	84 Participants n=143 Participants	352 Participants n=496 Participants
Race (NIH/OMB) More than one race	3 Participants n=177 Participants	0 Participants n=176 Participants	0 Participants n=143 Participants	3 Participants n=496 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=177 Participants	2 Participants n=176 Participants	0 Participants n=143 Participants	4 Participants n=496 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=177 Participants	2 Participants n=176 Participants	1 Participants n=143 Participants	3 Participants n=496 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	175 Participants n=177 Participants	172 Participants n=176 Participants	142 Participants n=143 Participants	489 Participants n=496 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=177 Participants	2 Participants n=176 Participants	0 Participants n=143 Participants	4 Participants n=496 Participants

PRIMARY outcome

Timeframe: 28-days post booster vaccination

Population: Moderna group:By day 28 1 participant was lost to follow-up and 1 had withdrawn Novavax: 4 people missed their visit for the day 28 blood draw and 1 was a withdrawal.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=175 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=171 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination	6792 binding antibody units (BAU/mL) Interval 6191.0 to 7451.0	3179 binding antibody units (BAU/mL) Interval 2854.0 to 3541.0	—

PRIMARY outcome

Timeframe: Total incidence of solicited reactions will be measured for 7 days post booster vaccination

Population: Solicited local and systemic reactions were collected for 7 days post-vaccination using a study-specific questionnaire. Outcomes are reported as both the number of participants in each arm and the percentage of participants in that arm experiencing reactions by severity grade. Reactions were graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild (does not interfere with activity); Grade 2 = moderate (may require non-narcotic analgesia); Grade 3 = severe (limits or prevents daily activity);

Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination. Reactogenicity was graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild and does not interfere with activity; Grade 2 = moderate or requiring repeated non-narcotic analgesia; Grade 3 = severe, limiting or preventing daily activity; Grade 4 = potentially life-threatening, requiring ER visit or hospitalisation.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Total Incidence of Solicited Reactions (Systemic and Local) Axillary Lymphadenopathy · Grade 1 (Mild)	21 Participants	13 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Redness · Grade 4 Potentially Life Threatening	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Swelling · Grade 0 no symptoms	157 Participants	172 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Swelling · Grade 1 (Mild)	9 Participants	3 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Swelling · Grade 2 Moderate	9 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Swelling · Grade 3 Severe	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Vomiting · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Vomiting · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Swelling · Grade 4 Potentially Life Threatening	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Hard · Grade 0 no symptoms	157 Participants	171 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Hard · Grade 1 (Mild)	14 Participants	4 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Hard · Grade 2 Moderate	5 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Hard · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Hard · Grade 4 Potentially Life Threatening	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Axillary Lymphadenopathy · Grade 0 no symptoms	149 Participants	162 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Axillary Lymphadenopathy · Grade 2 Moderate	7 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Axillary Lymphadenopathy · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Diarrhoea · Grade 0 no symptoms	163 Participants	163 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Diarrhoea · Grade 1 (Mild)	12 Participants	11 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Axillary Lymphadenopathy · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Warmth · Grade 0 no symptoms	119 Participants	146 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Warmth · Grade 1 (Mild)	55 Participants	29 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Itch · Grade 1 (Mild)	17 Participants	4 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Itch · Grade 2 Moderate	0 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Itch · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Itch · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fever · Grade 0 no symptoms	173 Participants	172 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fever · Grade 1 (Mild)	3 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Warmth · Grade 2 Moderate	3 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Warmth · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Warmth · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Itch · Grade 0 no symptoms	160 Participants	170 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Vomiting · Grade 2 Moderate	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fever · Grade 2 Moderate	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fever · Grade 3 Severe	0 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fever · Grade 4 Potentially Life Threatening	0 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Nausea · Grade 0 no symptoms	147 Participants	159 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Nausea · Grade 1 (Mild)	24 Participants	14 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Nausea · Grade 2 Moderate	6 Participants	3 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Nausea · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Nausea · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Vomiting · Grade 0 no symptoms	173 Participants	174 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Vomiting · Grade 1 (Mild)	4 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Pain · Grade 0 no symptoms	53 Participants	113 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Pain · Grade 1 (Mild)	105 Participants	61 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Pain · Grade 2 Moderate	19 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Pain · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Pain · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Tenderness · Grade 0 no symptoms	33 Participants	86 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Tenderness · Grade 1 (Mild)	80 Participants	72 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Tenderness · Grade 2 Moderate	60 Participants	16 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Tenderness · Grade 3 Severe	4 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Tenderness · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Diarrhoea · Grade 2 Moderate	2 Participants	2 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Redness · Grade 0 no symptoms	164 Participants	167 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Redness · Grade 1 (Mild)	6 Participants	6 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Redness · Grade 2 Moderate	5 Participants	3 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Redness · Grade 3 Severe	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Headache · Grade 3 Severe	0 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Headache · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fatigue/Malaise · Grade 0 no symptoms	76 Participants	106 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fatigue/Malaise · Grade 1 (Mild)	54 Participants	44 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fatigue/Malaise · Grade 2 Moderate	42 Participants	22 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fatigue/Malaise · Grade 3 Severe	5 Participants	4 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Fatigue/Malaise · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Muscle pain · Grade 0 no symptoms	94 Participants	140 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Muscle pain · Grade 1 (Mild)	63 Participants	31 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Muscle pain · Grade 2 Moderate	19 Participants	4 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Muscle pain · Grade 3 Severe	1 Participants	1 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Muscle pain · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Joint pain · Grade 0 no symptoms	128 Participants	157 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Joint pain · Grade 1 (Mild)	36 Participants	16 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Joint pain · Grade 2 Moderate	12 Participants	3 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Joint pain · Grade 3 Severe	1 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Joint pain · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Diarrhoea · Grade 3 Severe	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Diarrhoea · Grade 4 Potentially Life Threatening	0 Participants	0 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Headache · Grade 0 no symptoms	81 Participants	127 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Headache · Grade 1 (Mild)	61 Participants	40 Participants	—
Total Incidence of Solicited Reactions (Systemic and Local) Headache · Grade 2 Moderate	35 Participants	8 Participants	—

SECONDARY outcome

Timeframe: Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination

Population: One person in the Moderna group didn't have a blood taken at baseline

Serum samples collected at baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination from the two intervention groups and the control group will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA . Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination Baseline anti-spike IgG GMC (95% CI)	1418 binding antibody units (BAU/mL) Interval 1222.0 to 1646.0	1434 binding antibody units (BAU/mL) Interval 1257.0 to 1636.0	1182 binding antibody units (BAU/mL) Interval 1003.0 to 1392.0
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination 28 day anti-spike IgG GMC (95% CI) (Note, controls did not have blood taken at 28 days)	6792 binding antibody units (BAU/mL) Interval 6191.0 to 7452.0	3179 binding antibody units (BAU/mL) Interval 2854.0 to 3541.0	—
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination 6 month anti-spike IgG GMC (95% CI)	2451 binding antibody units (BAU/mL) Interval 2189.0 to 2745.0	1601 binding antibody units (BAU/mL) Interval 1424.0 to 1801.0	1108 binding antibody units (BAU/mL) Interval 931.0 to 1320.0
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination 12 month anti-spike IgG GMC (95% CI)	2047 binding antibody units (BAU/mL) Interval 1830.0 to 2289.0	1579 binding antibody units (BAU/mL) Interval 1405.0 to 1775.0	1346 binding antibody units (BAU/mL) Interval 1147.0 to 1580.0
SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination 18 month anti-spike IgG GMC (95% CI)	4059 binding antibody units (BAU/mL) Interval 3415.0 to 4825.0	3103 binding antibody units (BAU/mL) Interval 2616.0 to 3681.0	3186 binding antibody units (BAU/mL) Interval 2560.0 to 3964.0

SECONDARY outcome

Timeframe: Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination

Population: No Day 28 samples collected from control group as they did not receive any vaccine.

Neutralising antibody levels will be measured using the GenScript® cPass sVNT, which reports inhibition relative to a positive control. Results are expressed as concentrations (U/mL) and summarised as geometric mean concentrations (GMCs) with 95% CIs.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) Baseline Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI)	45745 U/mL Interval 38942.0 to 53736.0	48790 U/mL Interval 42339.0 to 56223.0	63280 U/mL Interval 54378.0 to 73638.0
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) 28 days Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI)	224397 U/mL Interval 204299.0 to 246472.0	96581 U/mL Interval 86417.0 to 107941.0	—
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) 6 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI)	92355 U/mL Interval 81954.0 to 104077.0	63682 U/mL Interval 56541.0 to 71724.0	48556 U/mL Interval 41569.0 to 56716.0
SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) 12 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI)	46494 U/mL Interval 40992.0 to 52734.0	36869 U/mL Interval 32362.0 to 41936.0	33932 U/mL Interval 28989.0 to 39719.0

SECONDARY outcome

Timeframe: Baseline (pre booster), 6,12 and 18-months post booster vaccination

A subset of samples (20%) from all timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination

Population: No Day 28 samples collected for Control group as no vaccine were given.

Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in whole blood and then IFN-γ production will be measured using Enzyme-Linked ImmunoSorbent Assay (ELISA). Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=89 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=89 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=73 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL Day 28	1.10 IU/mL Interval 0.87 to 1.38	0.98 IU/mL Interval 0.81 to 1.17	—
Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL Baseline	0.39 IU/mL Interval 0.3 to 0.5	0.45 IU/mL Interval 0.35 to 0.57	0.57 IU/mL Interval 0.46 to 0.71

SECONDARY outcome

Timeframe: Baseline (pre booster), 6, 12 and 18-months post booster vaccination

IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs) stimulated with SARS-CoV-2 specific peptides. Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (pre booster), 6, 12 and 18 -months post booster vaccination

Frequency of cytokine-expressing T cells will be assessed on a subset (50%) of participants using Flow cytometry (intracellular staining) on PBMCs samples stimulated with SARS-CoV-2 specific peptides. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (pre booster), 6, 12 and 18-months post booster vaccination

Cytokine concentrations following PBMCs stimulation will be assessed on a subset (50%) of participants using multiplex cytokine assays. Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days-post booster vaccination

Unsolicited adverse events were collected for 28 days post-booster. Results are reported as the number and percentage of randomised participants in each arm who experienced an unsolicited AE.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Incidence of Unsolicited Adverse Events (AE) Headache	1 Participants	0 Participants	—
Incidence of Unsolicited Adverse Events (AE) Supraventricular tachycardia	1 Participants	0 Participants	—
Incidence of Unsolicited Adverse Events (AE) Acne	1 Participants	0 Participants	—
Incidence of Unsolicited Adverse Events (AE) Mouth ulceration	1 Participants	0 Participants	—
Incidence of Unsolicited Adverse Events (AE) Heavy menstrual bleeding	0 Participants	1 Participants	—
Incidence of Unsolicited Adverse Events (AE) Nasal congestion	0 Participants	1 Participants	—
Incidence of Unsolicited Adverse Events (AE) Administration site pain	0 Participants	1 Participants	—
Incidence of Unsolicited Adverse Events (AE) Road traffic accident	0 Participants	2 Participants	—
Incidence of Unsolicited Adverse Events (AE) Tinnitus	0 Participants	1 Participants	—
Incidence of Unsolicited Adverse Events (AE) No reported AE	168 Participants	168 Participants	—
Incidence of Unsolicited Adverse Events (AE) Chest pain	2 Participants	1 Participants	—
Incidence of Unsolicited Adverse Events (AE) Dyspnoea	3 Participants	1 Participants	—

SECONDARY outcome

Timeframe: 3 months post booster vaccination

Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as number of medically attended adverse events. Serious adverse events (SAEs) are reported separately.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Incidence of Medically Attended Adverse Events (AE)	0 Medically attended adverse events	1 Medically attended adverse events	0 Medically attended adverse events

SECONDARY outcome

Timeframe: 24 months post booster vaccination

Serious adverse events (SAEs) were collected throughout the 24-month follow-up period after booster vaccination. Data are reported as the number of SAEs occurring in each randomised arm.

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Incidence of Serious Adverse Events (SAE)	5 Serious adverse events	8 Serious adverse events	8 Serious adverse events

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months post booster vaccination

SARS-CoV-2 infections were recorded throughout the 24-month follow-up period based on participant self-report of a positive RAT or PCR test. Data are reported as the number of infections occurring in each study arm during this period

Outcome measures

Outcome measures
Measure	Bivalent Moderna (mRNA-1273.214) n=177 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Control Group- no Vaccine n=143 Participants Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
SARS-CoV-2 Infections	101 Reported SARS-CoV-2 infections	85 Reported SARS-CoV-2 infections	78 Reported SARS-CoV-2 infections

Adverse Events

Bivalent Moderna (mRNA-1273.214)

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Novavax

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Controls

Serious events: 8 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Bivalent Moderna (mRNA-1273.214) n=177 participants at risk Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]). Bivalent Moderna: A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.	Novavax n=176 participants at risk Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms). Novavax: A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.	Controls n=143 participants at risk Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.
Skin and subcutaneous tissue disorders Acne	0.56% 1/177 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
General disorders Administration site pain	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Infections and infestations Cellulitis	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.70% 1/143 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Surgical and medical procedures Abortion induced	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Reproductive system and breast disorders Cervix carcinoma	0.56% 1/177 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
General disorders Chest pain	1.1% 2/177 • Number of events 2 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 3/177 • Number of events 3 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Nervous system disorders Headache	0.56% 1/177 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Reproductive system and breast disorders Heavy menstrual bleeding	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Infections and infestations Laryngitis	0.56% 1/177 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Gastrointestinal disorders Mouth ulceration	0.56% 1/177 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/176 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
Ear and labyrinth disorders Tinnitus	0.00% 0/177 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.57% 1/176 • Number of events 1 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination	0.00% 0/143 • Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination

Additional Information

Kathryn Bright

Murdoch Childrens Research Institute

Phone: +61 3 99366656

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place