385. Safety and Immunogenicity of a Variant-adapted Bivalent (Original/Omicron BA.4/BA.5) BNT162b2 COVID-19 Vaccine Given as a Booster (Dose 4) to 5- to 11-Year-Old Children Who Previously Received 3 Doses of Original BNT162b2

BACKGROUND: A variant-adapted bivalent BNT162b2 mRNA vaccine (bivalent BNT162b2) comprising original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins is authorized by the US FDA from 6 months of age as a primary series or as booster doses. We studied whether bivalent BNT162b2 booster generates improved immune responses against Omicron BA.4/BA.5 and ancestral strains and had a comparable safety profile to original BNT162b2 in 5–11-year-olds. METHODS: This substudy is part of a phase 1/2/3 master study (NCT05543616) examining safety and immunogenicity of bivalent BNT162b2 in healthy children. The substudy group reported here is open label and evaluates a fourth dose with bivalent BNT162b2 10 μg (5 µg original; 5 µg BA.4/BA.5) in 5–11-year-olds who previously received 3 original BNT162b2 10 μg doses. Reactogenicity (7 day), and 1 month safety and immunogenicity were assessed. SARS-CoV-2 Omicron BA.4/BA.5 and ancestral strain neutralization titers post dose 4 were descriptive immunogenicity endpoints. The comparator group for immunogenicity assessments included 113 participants from the initial pediatric study (NCT04816643) who received 3 original BNT162b2 10 μg doses and who were matched by age and SARS-CoV-2 infection status. RESULTS: Of the 113 children who received bivalent BNT162b2, 50% were female, 58% White, and 58% SARS-CoV-2 positive at baseline. Median (range) time from dose 3 of original BNT162b2 to bivalent BNT162b2 was 5.5 (2.6−8.6) months. Bivalent BNT162b2 was well tolerated with mostly mild to moderate reactogenicity; no grade 4 events were observed (Figure). No serious adverse events were reported. The safety and tolerability profile was generally consistent with that of original BNT162b2. Bivalent BNT162b2 elicited higher neutralizing titers against Omicron BA.4/BA.5 and similar titers against the ancestral strain 1 month post dose 4 compared with original BNT162b2 at 1 month post dose 3 overall and in those who were SARS-CoV-2 positive (Table). [Figure: see text] [Figure: see text] CONCLUSION: In 5–11-year-olds, a booster (dose 4) of bivalent BNT162b2 10 µg had a similar safety profile to original BNT162b2 10 µg and induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers. These data support booster dosing with variant-adapted bivalent BNT162b2 in 5–11-year-olds. DISCLOSURES: Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lawrence Sher, MD, Pfizer Inc: Clinical Investigator Charu Sabharwal, MD, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Nicholas Kitchin, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Sungeen Hill, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Emily Wasserman, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Xia Xu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Emmanuel Walter, MD, Clinetic: Clinical Investigator|Iliad Biotechnologies: Advisor/Consultant|Moderna: Clinical Investigator|Najit Technologies: Clinical Investigator|Pfizer Inc: Clinical Investigator|Sequiris: Clinical Investigator|Vaxcyte: Advisor/Consultant Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Eric Simoes, MD DCH, Abbott Diagnostics: Advisor/Consultant|Abbvie Inc: Advisor/Consultant|Abbvie Inc: DSMB study section|AstraZeneca: Grant/Research Support|AstraZeneca: travel|Bill and Melinda Gates Foundation: Advisor/Consultant|Bill and Melinda Gates Foundation: Grant/Research Support|Bill and Melinda Gates Foundation: travel, DSMB study section|CDC: Advisor/Consultant|CDC: travel|GSK plc: Advisor/Consultant|GSK plc: DSMB study section|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Grant/Research Support|Merck & Co Inc: Grant/Research Support|National Institutes of Health: Grant/Research Support|National Institutes of Health: travel, DSMB study section|Novavax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: travel|Regeneron: Grant/Research Support|Roche: Grant/Research Support|Roche: travel|USAID: Advisor/Consultant|USAID: Grant/Research Support|USAID: travel|WHO: Advisor/Consultant|WHO: travel Kawsar R. Talaat, MD, Intralytix: Advisor/Consultant|Merck: Advisor/Consultant|NIAID: DSMB|Pfizer: Grant/Research Support|Pfizer: Pfizer contract with institution|Sanofi: Grant/Research Support|Takeda: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Lisa Moyer, BS, Pfizer: Employee|Pfizer: Stocks/Bonds Vrunda Parikh, PharmD, Pfizer: Employee|Pfizer: Stocks/Bonds Hua Ma, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Xingbin Wang, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds