Trial Outcomes & Findings for Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine (NCT NCT03300050)

Results Overview

Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited local reactions included: * Post LAIV dose: nasal congestion, rhinorrhea; * Post IIV dose: pain, redness, swelling.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

65 participants

Primary outcome timeframe

7 days after each vaccination (Days 1-8 and Days 85-92)

Results posted on

2021-02-21

Participant Flow

Participants were recruited from the community and enrolled at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA) and the Duke Early Phase Clinical Research Unit (Durham, NC, USA) between October 10, 2017, and November 27, 2017.

Participants were randomly assigned in a 4:3:1:3:2 ratio to one of five treatment groups. Randomization was blocked (block size 13) and stratified by site. Participants received two sequential study vaccinations, an initial priming dose on Day 1 followed by a booster dose on Day 85.

Participant milestones

Participant milestones
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL chimeric H8/1N1 live-attenuated influenza virus vaccine (cH8/1N1 LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03 (Adjuvant System 03)-adjuvanted chimeric H5/1N1 inactivated influenza virus vaccine (cH5/1N1 IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL AS03-adjuvanted chimeric H8/1N1 inactivated influenza vaccine (cH8/1N1 IIV) administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Study STARTED	20	15	5	16	10
Overall Study Received Treatment	19	14	3	15	10
Overall Study Received All Scheduled Treatments	16	13	2	15	10
Overall Study COMPLETED	17	13	2	15	9
Overall Study NOT COMPLETED	3	2	3	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL chimeric H8/1N1 live-attenuated influenza virus vaccine (cH8/1N1 LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03 (Adjuvant System 03)-adjuvanted chimeric H5/1N1 inactivated influenza virus vaccine (cH5/1N1 IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL AS03-adjuvanted chimeric H8/1N1 inactivated influenza vaccine (cH8/1N1 IIV) administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Overall Study Lost to Follow-up	2	1	0	0	1
Overall Study Withdrawal by Subject	1	1	1	0	0
Overall Study Death	0	0	1	0	0
Overall Study Not Eligible at Randomization	0	0	1	1	0

Baseline Characteristics

Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=20 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=15 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=5 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=16 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.	Total n=66 Participants Total of all reporting groups
Age, Continuous	29.9 years STANDARD_DEVIATION 5.3 • n=5 Participants	27.5 years STANDARD_DEVIATION 5.9 • n=7 Participants	25.0 years STANDARD_DEVIATION 3.7 • n=5 Participants	30.3 years STANDARD_DEVIATION 5.5 • n=4 Participants	29.3 years STANDARD_DEVIATION 4.6 • n=21 Participants	28.9 years STANDARD_DEVIATION 5.3 • n=10 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	10 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants	5 Participants n=21 Participants	41 Participants n=10 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	25 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	13 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants	10 Participants n=21 Participants	63 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants	7 Participants n=21 Participants	50 Participants n=10 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	13 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants

PRIMARY outcome

Timeframe: 7 days after each vaccination (Days 1-8 and Days 85-92)

Population: Participants who received the priming dose and booster dose

Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited local reactions included: * Post LAIV dose: nasal congestion, rhinorrhea; * Post IIV dose: pain, redness, swelling.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Any Local Reacton	10 Participants	2 Participants	0 Participants	11 Participants	1 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Nasal Congestion	4 Participants	1 Participants	0 Participants	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Rhinorrhea	8 Participants	2 Participants	0 Participants	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Pain	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	11 Participants	1 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Redness	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	1 Participants	0 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Prime Dose · Swelling	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	NA Participants Reaction not applicable for intranasal administration	1 Participants	0 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Any Local Reacton	10 Participants	1 Participants	0 Participants	8 Participants	0 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Nasal Congestion	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Rhinorrhea	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection	NA Participants Reaction not applicable for intramuscular injection
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Pain	10 Participants	1 Participants	0 Participants	8 Participants	0 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Redness	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited Local Reactions Within 7 Days Following Each Vaccination Post Booster Dose · Swelling	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 7 days after each vaccination (Days 1-8 and Days 85-92)

Population: Participants who received the priming dose and booster dose

Solicited adverse events were assessed by study staff for 60 minutes after each vaccination and and then by study participants daily for 7 days on a a diary card. Solicited general reactions included: * abdominal pain * arthralgia * cough * diarrhea * fatigue * fever * headache * myalgia * nausea * shivering * sore throat * vomiting * wheezing

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Any General Reaction	13 Participants	8 Participants	1 Participants	10 Participants	4 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Fever	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Shivering	3 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Fatigue	3 Participants	4 Participants	0 Participants	6 Participants	3 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Headache	7 Participants	4 Participants	1 Participants	6 Participants	2 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Myalgia	4 Participants	2 Participants	0 Participants	6 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Arthralgia	0 Participants	3 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Nausea	3 Participants	3 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Vomiting	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Abdominal Pain	2 Participants	2 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Diarrhea	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Sore Throat	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Cough	4 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Prime Dose: Wheezing	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Any General Reaction	10 Participants	5 Participants	0 Participants	5 Participants	1 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose : Fever	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Shivering	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Fatigue	8 Participants	3 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose : Headache	4 Participants	4 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Myalgia	5 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Arthralgia	4 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Nausea	3 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Vomiting	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Abdominal Pain	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Diarrhea	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Sore Throat	3 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Cough	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Solicited General Reactions Within 7 Days Following Each Vaccination Post Booster Dose: Wheezing	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 28 days after each vaccination (Days 1 to 28 and Days 85 to 113)

Population: Participants who received at least one study vaccination

Unsolicited adverse events (AEs) are any AEs reported spontaneously by the participant, observed by the study personnel during study visits or those identified during review of medical records or source documents, such as diary cards. Participants were asked to record any unsolicited symptoms or other illness description in their diary card during the 28 days after each vaccination. All AEs, including clinical laboratory test results, were assessed by a study clinician and the study subject (as applicable) to quantify severity using a protocol-defined grading system as mild (mild symptoms, easily tolerated, not interfering with daily activities), moderate (causing some interference with daily activity), or severe (severe symptoms that prevent normal every day activities). The investigator assessed the relationship between study vaccines and the occurrence of each AE using clinical judgment.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Any adverse events	10 Participants	8 Participants	1 Participants	6 Participants	5 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination AEs related to study vaccine	5 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Mild adverse events	6 Participants	3 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Mild AEs related to study vaccine	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Moderate adverse events	3 Participants	4 Participants	1 Participants	3 Participants	2 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Moderate AEs related to study vaccine	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Severe adverse events	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Unsolicited Adverse Events Within 28 Days Following Any Vaccination Severe AEs related to study vaccine	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Days 8, 29, 85, 92, and 113

Population: Participants who received at least one study vaccination

Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: * BUN: \> 26 mg/dL * Creatinine: \> 1.7 mg/dL * ALT, AST: \> 2.5 × upper limit of normal (ULN) * Hemoglobin: \< 11.0 g/dL (females) or \< 12.5 g/dL (males) or change from baseline \> 1.5 g/dL * WBC: \> 15,000 cell/mm³ or \< 2,500 cell/mm³ * Lymphocytes: \< 750 cell/mm³ * ANC: \< 1,500 cell/mm³ * Eosinophils: \> 1,500 cell/mm³ * Platelets: \< 125,000 cell/mm³

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Hemoglobin	0 Participants	2 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Hemoglobin change from baseline	3 Participants	1 Participants	2 Participants	3 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Platelets	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 White blood cell count	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Absolute neutrophil count	5 Participants	1 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Lymphocytes	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Basophils	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Monocytes	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Eosinophils	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Red blood cells	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Creatinine	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Blood urea nitrogen	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 BUN to creatinine ratio	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Alanine aminotransferase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Day 8 to Day 113 Asparate aminotransferase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Through Day 113 (28 days post-dose 2)

Population: Participants who received at least one study vaccination

An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by polymerase chain reaction (PCR) assay. An SAE is an AE that met any of the following: * Death * Life threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * Results in congenital anomaly/birth defect * An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113 SAEs	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113 MAEs	6 Participants	2 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113 LC-ILIs	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to Day 113 pIMDs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 9 (6 months post-dose 2) and Month 15 (12 months post-dose 2)

Population: Participants who received at least one study vaccination

Hematological and biochemical parameters assessed included hemoglobin, platelets, red blood cells, white blood cells (WBC), absolute neutrophil count (ANC), lymphocytes, monocytes, eosinophils, basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN) and BUN-to-creatinine ratio. Grading of laboratory parameters was based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials as Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe), or Grade 4 (Potentially life-threatening). Grade 2 or higher: * BUN: \> 26 mg/dL * Creatinine: \> 1.7 mg/dL * ALT, AST: \> 2.5 × upper limit of normal (ULN) * Hemoglobin: \< 11.0 g/dL (females) or \< 12.5 g/dL (males) or change from baseline \> 1.5 g/dL * WBC: \> 15,000 cell/mm³ or \< 2,500 cell/mm³ * Lymphocytes: \< 750 cell/mm³ * ANC: \< 1,500 cell/mm³ * Eosinophils: \> 1,500 cell/mm³ * Platelets: \< 125,000 cell/mm³

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Hemoglobin	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Hemoglobin change from baseline	0 Participants	1 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Platelets	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 White blood cell count	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Absolute neutrophil count	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Lymphocytes	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Basophils	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Monocytes	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Eosinophils	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Red blood cells	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Creatinine	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Blood urea nitrogen	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 BUN to creatinine ratio	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Alanine aminotransferase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any Grade 2 or Higher Hematological and Biochemical Laboratory Abnormalities From Month 9 to Month 15 Asparate aminotransferase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose to end of study, 588 days (21 months; 18 months post-dose 2)

Population: Participants who received at least one study vaccination

An MAE is an event for which the participant received medical attention such as hospitalization, an emergency room visit, or a visit to or from medical personnel. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. LC-ILI is defined as at least 1 systemic symptom (fever or myalgia) AND at least 1 respiratory symptom (cough or sore throat), confirmed by PCR assay. An SAE is an AE that met any of the following: * Death * Life threatening * Required inpatient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * Resulted in congenital anomaly/birth defect * An important medical event that may jeopardize the well-being of the subject or require medical or surgical intervention to prevent an above outcome.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study SAEs	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study MAEs	7 Participants	4 Participants	0 Participants	4 Participants	4 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study LC-ILIs	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With a Medically Attended Event (MAE), Laboratory-Confirmed Influenza-like Illness (LC-ILI), Potential Immune-mediated Disease (pIMD), or Serious Adverse Event (SAE) up to End of Study pIMDs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1 to 5

Population: Participants who received LAIV (Groups 1, 2, and 3) with evaluable samples

To detect viral shedding participants who received LAIV vaccine or intranasal sterile saline as the prime dose had nasal and oropharyngeal swabs collected on Days 1 to 5. Influenza type A virus ribonucleic acid (RNA) was detected using reverse transcription polymerase chain reaction (RT-PCR).

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 Overall	7 Participants	8 Participants	0 Participants	—	—
Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 Day 2	7 Participants	4 Participants	0 Participants	—	—
Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 Day 3	1 Participants	1 Participants	0 Participants	—	—
Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 Day 4	0 Participants	0 Participants	0 Participants	—	—
Number of Participants in Groups 1, 2, and 3 With Detectable Influenza A Virus in Nasal and Oropharyngeal Swabs on Days 1 to 5 Day 5	0 Participants	3 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Days 1 to 5

Population: Participants who received LAIV (Groups 1, 2, and 3) and tested positive for influenza A virus by RT-PCR at any time during the 5 days post LAIV dose and with evaluable samples

To study virus infectivity, nasal and oropharyngeal swab specimens that tested influenza A positive by RT-PCR were further tested for viability of virus in Madin Darby canine kidney (MDCK) cell culture and stained with monoclonal antibody specific to the cH8/1N1 LAIV virus to confirm detected virus is of vaccine origin.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=7 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=7 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination Overall	0 Participants	0 Participants	—	—	—
Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination Day 2	0 Participants	0 Participants	—	—	—
Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination Day 3	0 Participants	0 Participants	—	—	—
Number of Participants in Groups 1, 2, and 3 With Viable Vaccine Virus in Cell Culture Through 5 Days Post-vaccination Day 5	—	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Population: Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Anti-H1 hemagglutinin (HA) stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 \[H6N1\]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 \[H1N1\]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. Seropositivity rate was defined as the percentage of participants with an antibody titer of at least the cut-off for the assay; ≥ 65.3 EU/mL.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity Baseline (pre-vaccination)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity Month 1 (28 days post-dose 1)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity Month 4 (28 days post-dose 2)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity Month 9 (6 months post-dose 2)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Serum Anti-H1 Hemagglutinin Stalk Immunoglobulin G Antibody Seropositivity Month 15 (12 months post-dose 2)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Population: Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 \[H6N1\]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 \[H1N1\]) . Titers are expressed as ELISA units (EU) per mL and were calculated on the basis of an internal standard to which units were arbitrarily assigned. The lower limit of quantitation (LLOQ) for the assay was 65.3 EU/mL.

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Baseline (pre-vaccination)	11503 EU/mL Interval 7698.0 to 17187.0	10213 EU/mL Interval 6559.0 to 15903.0	12966 EU/mL Interval 2459.0 to 68377.0	12028 EU/mL Interval 6658.0 to 21729.0	8615 EU/mL Interval 5517.0 to 13453.0
Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 1 (28 days post-dose 1)	11337 EU/mL Interval 7790.0 to 16499.0	10347 EU/mL Interval 6810.0 to 15721.0	11832 EU/mL Interval 2593.0 to 53992.0	84207 EU/mL Interval 63756.0 to 111219.0	7975 EU/mL Interval 5317.0 to 11961.0
Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 4 (28 days post-dose 2)	62238 EU/mL Interval 44507.0 to 87034.0	22073 EU/mL Interval 14577.0 to 33423.0	10628 EU/mL Interval to 5749922.0 \< LLOQ (65.3 EU/mL)	62992 EU/mL Interval 46931.0 to 84549.0	9226 EU/mL Interval 5791.0 to 14696.0
Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 9 (6 months post-dose 2)	19955 EU/mL Interval 13334.0 to 29863.0	10846 EU/mL Interval 7108.0 to 16549.0	8364 EU/mL Interval to 12544501.0 \< LLOQ (65.3 EU/mL)	31228 EU/mL Interval 21153.0 to 46101.0	7043 EU/mL Interval 4019.0 to 12345.0
Geometric Mean Titer of Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 15 (12 months post-dose 2)	16046 EU/mL Interval 10632.0 to 24218.0	13470 EU/mL Interval 8300.0 to 21860.0	16195 EU/mL	27323 EU/mL Interval 17736.0 to 42092.0	6825 EU/mL Interval 4132.0 to 11272.0

SECONDARY outcome

Timeframe: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Population: Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 \[H6N1\]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 \[H1N1\]) .

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 1 (28 days post-dose 1)	0.0 percentage of participants Interval 0.0 to 17.6	0.0 percentage of participants Interval 0.0 to 23.2	0.0 percentage of participants Interval 0.0 to 70.8	80.0 percentage of participants Interval 51.9 to 95.7	0.0 percentage of participants Interval 0.0 to 30.8
Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 4 (28 days post-dose 2)	75.0 percentage of participants Interval 47.6 to 92.7	15.4 percentage of participants Interval 1.9 to 45.4	0.0 percentage of participants Interval 0.0 to 84.2	57.1 percentage of participants Interval 28.9 to 82.3	0.0 percentage of participants Interval 0.0 to 30.8
Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 9 (6 months post-dose 2)	6.7 percentage of participants Interval 0.2 to 31.9	0.0 percentage of participants Interval 0.0 to 24.7	0.0 percentage of participants Interval 0.0 to 84.2	21.4 percentage of participants Interval 4.7 to 50.8	0.0 percentage of participants Interval 0.0 to 33.6
Percentage of Participants With a ≥ 4-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 15 (12 months post-dose 2)	7.1 percentage of participants Interval 0.2 to 33.9	15.4 percentage of participants Interval 1.9 to 45.4	0.0 percentage of participants	23.1 percentage of participants Interval 5.0 to 53.8	0.0 percentage of participants Interval 0.0 to 30.8

SECONDARY outcome

Timeframe: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Population: Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 \[H6N1\]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 \[H1N1\]) .

Outcome measures

Outcome measures
Measure	Group 1: cH8/1N1 LAIV and cH5/1N1 IIV + Adjuvant n=19 Participants Participants received 0.5 mL cH8/1N1 live-attenuated influenza virus vaccine (LAIV) administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 inactivated influenza virus vaccine (IIV) administered as an intramuscular injection on Day 85.	Group 2: cH8/1N1 LAIV and cH5/1N1 IIV n=14 Participants Participants received 0.5 mL cH8/1N1 LAIV administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 3: Placebo n=3 Participants Participants received 0.5 mL normal saline administered as 0.25 mL drops per nostril on Day 1 followed by 0.5 mL phosphate buffered saline (PBS) administered as an intramuscular injection on Day 85.	Group 4: cH8/1N1 IIV + Adjuvant and cH5/1N1 IIV + Adjuvant n=15 Participants Participants received 0.5 mL AS03-adjuvanted cH8/1N1 IIV administered as an intramuscular injection on Day 1 followed by 0.5 mL AS03-adjuvanted cH5/1N1 IIV administered as an intramuscular injection on Day 85.	Group 5: Placebo n=10 Participants Participants received 0.5 mL PBS administered as an intramuscular injection on Day 1 followed by 0.5 mL PBS administered as an intramuscular injection on Day 85.
Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 1 (28 days post-dose 1)	0.0 percentage of participants Interval 0.0 to 17.6	0.0 percentage of participants Interval 0.0 to 23.2	0.0 percentage of participants Interval 0.0 to 70.8	33.3 percentage of participants Interval 11.8 to 61.6	0.0 percentage of participants Interval 0.0 to 30.8
Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 4 (28 days post-dose 2)	25.0 percentage of participants Interval 7.3 to 52.4	0.0 percentage of participants Interval 0.0 to 24.7	0.0 percentage of participants Interval 0.0 to 84.2	14.3 percentage of participants Interval 1.8 to 42.8	0.0 percentage of participants Interval 0.0 to 30.8
Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 9 (6 months post-dose 2)	0.0 percentage of participants Interval 0.0 to 21.8	0.0 percentage of participants Interval 0.0 to 24.7	0.0 percentage of participants Interval 0.0 to 84.2	0.0 percentage of participants Interval 0.0 to 23.2	0.0 percentage of participants Interval 0.0 to 33.6
Percentage of Participants With a ≥ 10-fold Increase From Baseline in Serum Anti-H1 Hemagglutinin Stalk IgG Antibodies Month 15 (12 months post-dose 2)	0.0 percentage of participants Interval 0.0 to 23.2	0.0 percentage of participants Interval 0.0 to 24.7	0.0 percentage of participants	0.0 percentage of participants Interval 0.0 to 24.7	0.0 percentage of participants Interval 0.0 to 30.8

SECONDARY outcome

Timeframe: Baseline (pre-dose 1), Month 1 (28 days post-dose 1), Month 4 (28 days post-dose 2), Month 9 (6 months post-dose 2), and Month 15 (12 months post-dose 2)

Population: Participants in the per-protocol population with available data at each time point. The per protocol population included all participants who received at least 1 vaccination and with no major deviations, including those considered likely to affect the immune response; data were included up to the time of the observed deviation event.

Anti-H1 hemagglutinin stalk immunoglobulin G (IgG) was quantified using an enzyme-linked immunosorbent assay (ELISA). The ELISA measured IgG antibodies against the H1 stalk domain by using a chimeric protein containing an exotic H6 hemagglutinin head domain that the vaccinees have not previously been exposed to (strain A/mallard/Sweden/81/02 \[H6N1\]) and the same H1 stalk domain as expressed by the vaccine (strain A/California/04/09 \[H1N1\]). Mean geometric increase represents the fold-rise in antibody titer from baseline to each post-baseline time point (ratio of post-baseline titer to Baseline titer).