362. 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 Toddlers and Children 6 Months to &lt; 5 Years of Age Who Previously Received Original BNT162b2 as a 3-Dose Primary Series
Authors: Sher Lawrence , Sabharwal Charu , Kitchin Nicholas , Kofi Boakya-Appiah Justice , Xu Xia , Walter Emmanuel , Maldonado Yvonne A , Munoz Flor M , Englund Janet A , Talaat Kawsar R , Senders Shelly , Kamidani Satoshi , Barnett Elizabeth , Paulsen Grant C , Moyer Lisa , Parikh Vrunda , Ma Hua , Wang Xingbin , Koury Kenneth , Anderson Annaliesa S , Swanson Kena A , Gurtman Alejandra C , Gruber William C 
Published: November 2023

Abstract

Background
A variant-adapted bivalent BNT162b2 vaccine (bivalent BNT162b2) comprised of original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins was developed to improve protection against SARS-CoV-2 variants. Bivalent BNT162b2 is authorized by the US FDA from 6 months (mo) old; for children 6 mo to &lt; 5 years (y), it is authorized as a 3-dose primary series and as a fourth dose (first booster).

Methods
This substudy is part of a phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of bivalent BNT162b2. The group reported here is open label and evaluates a fourth dose (first booster) with bivalent BNT162b2 3 μg in children 6 mo to &lt; 5 y who previously received 3 original BNT162b2 3 μg doses. Reactogenicity (7 day), and 1 mo safety and immunogenicity for a subset of 60 participants were assessed. Descriptive immunogenicity endpoints included SARS-CoV-2 Omicron BA.4/BA.5 and ancestral strain neutralization responses post dose 4. A comparator group for immunogenicity included 60 participants, matched by age and SARS-CoV-2 infection status, from the initial pediatric study (NCT04816643) who received 3 original BNT162b2 3 μg doses without a booster.

Results
Of children 6 mo to &lt; 5 y old (6 mo to &lt; 2 y, n = 24; 2 y to &lt; 5 y, n = 36) who received bivalent BNT162b2 as a fourth dose, 50% were male, 58% White, 5% Black, 15% Asian, 22% multiracial, 25% Hispanic/Latino; 28.3% had evidence of past SARS-CoV-2 infection. Median time from dose 3 of original BNT162b2 to bivalent BNT162b2 was 6.5 mo. Bivalent BNT162b2 was generally well tolerated with mostly mild to moderate reactogenicity and minimal fever (Figure), few reported adverse events (AEs), no serious AEs, and no new safety signals identified. Bivalent BNT162b2 elicited higher neutralizing titers against Omicron BA.4/BA.5 and similar titers against ancestral strain 1 mo post dose 4 compared with original BNT162b2 1 mo post dose 3 (Table). Robust immune responses were observed regardless of previous SARS-CoV-2 infection status.

Conclusion
A booster (dose 4) of bivalent BNT162b2 had a similar safety profile to original BNT162b2 and induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers in children 6 mo to &lt; 5 y. These descriptive data reinforce the importance of a variant-adapted bivalent COVID-19 booster dose in this age group.

Disclosures
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 Justice Kofi Boakya-Appiah, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Xia Xu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds 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 Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member 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 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 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 Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: 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