Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents
Authors: Samir Arora
Aaron Hartman
Kathrin U Jansen
Michael Dever
Kenneth Koury
Robert Frenck
William Randall
Timothy Jennings
Shelly Senders
Gretchen Crook
Douglas Denham
Hector Rodriguez
David Butuk
Susan Mather
Xia Xu
Brandon Essink
Donald Brandon
William C Gruber
Emmanuel B Walter
Özlem Türeci
David Cooper
Charles Harper
Fadi Chalhoub
Matthew Davis
Julia Garcia-Diaz
C4591001 Clinical Trial Group
Ruth Bailey
Warren V Kalina
Emmanuel Walter
Kena A Swanson
Suchet Patel
Richard Rupp
Donald M Brandon
John Vanchiere
Stephen J Thomas
Nicholas Kitchin
James Peterson
Hua Ma
Onyema Ogbuagu
Philip R Dormitzer
Robert W Frenck Jr
Nicola P Klein
Daniel Finn
Stephen Thomas
Judith Absalon
Dina B Tresnan
Alejandra Gurtman
Uğur Şahin
John L Perez
David Fried
Nicola Klein
Stephen Lockhart
Shane Christensen
Journal: New England Journal of Medicine (2021)
Discipline: CLINICAL MEDICINE
Keywords: vaccine; SARS-CoV-2; adolescents; safety; efficacy
Affiliations: From Cincinnati Children's Hospital, Cincinnati (R.W.F.); Kaiser Permanente Vaccine Study Center, Oakland (N.P.K.), and the California Research Foundation, San Diego (D.M.B.) - both in California; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); Vaccine Research and Development, Pfizer, Pearl River (A.G., J.A., K.A.S., K.K., W.V.K., D.C., P.R.D., K.U.J., W.C.G.), and SUNY Upstate Medical University, Syracuse (S.J.T.) - both in New York; Vaccine Research and Development (J.L.P., H.M., X.X.) and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Duke Human Vaccine Institute, Durham, NC (E.B.W.); Senders Pediatrics, South Euclid, OH (S.S.); Clinical Research Professionals, Chesterfield, MO (T.J.); BioNTech, Mainz, Germany (Ö.T., U.Ş.); and Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Groton, CT (D.B.T.).

Abstract:  Background: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. Methods: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 μg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed. Results: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). Conclusions: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.). 

Retracted: No

PubPeer comments:
 It has been reported [(link)] that the 12-15 cohort was recruited for this study separately from the 16-25 cohort, whose data is extracted from a previous adult trial. If that is correct, the authors should mention that point in the methods and discuss the possible biases it induces, in particular what differences (if any) were present in the recruitment process (up to randomization) between the (US-based) 12-15 cohort and the immunogenicity subset of the 16-25 cohort. ,