Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Authors: Samir Arora
Aaron Hartman
Teresa Sligh
Kathrin U Jansen
Michael Dever
Sedat Altƒ±n
Salma Saiger
Timothy Jennings
Michael Stephens
Susan Mather
Gonzalo P√©rez Marc
Brandon Essink
Steven Katzman
Donald Brandon
James McMurray
Sƒ±la Akhan
Matthew Davis
Emily Morawski
Tracy Klein
Ping Li
Hayes Williams
Michael Lillestol
Ismail Balik
Helen Stacey
Stephen J Thomas
Mark Koch
Martin Schear
Serap Simsek Yavuz
Nathan Segall
Daniel Brune
Uƒüur ≈ûahin
Iftahar K√∂ksal
Fernando Polack
Darrell Herrington
Paul Matherne
Steven Reynolds
Stephan Sharp
William Seger
Robert Riesenberg
Jonathan Wilson
Nicola Klein
Andreas Eich
David Ensz
Carla Greenbaum
Edward Tyler L Wadsworth
Sylvia Shoffner
Elizabeth Barnett
Mohamed Al-Ibrahim
Jamshid Saleh
Mary Beth Earl Manning
Joseph Yozviak
Jeffrey Rosen
Oƒüuz Karabay
Michael Koren
John Rubino
Bruce Rankin
Paul Bradley
Fehmi Tabak
Michael Dunn
Sybille Baumann-Noss
Julia Garcia-Diaz
Stephen Grubb
C4591001 Clinical Trial Group
Axel Schaefer
Robert Heller
Emmanuel Walter
Kena A Swanson
Kawsar Talaat
Armin Schultz
Susann Varano
George Raad
Nicholas Kitchin
Suzanne Fussell
Onyema Ogbuagu
Mark Leibowitz
Abram Burgher
Daniel Finn
Dina B Tresnan
Randle Middleton
Robert Salata
Alejandra Gurtman
Van Tran
Dany Musungaie
Christopher Lucasti
Martin Martin
Serhat √únal
Howard Schwartz
Stephen Thomas
Robert Finberg
Matthias Luttermann
Richard Glover
Judith Absalon
Paul Pickrell
Kenneth Koury
Laurence Chu
Timothy Albertson
William Randall
Veronica Fragoso
Cristiano Zerbini
Haylene Nell
Romina Libster
Gretchen Crook
Diego Wappner
David Butuk
Michael Levin
Patricia Winokur
Ali Mert
Jeffrey Kingsley
Charles Andrews
Charles Harper
Fadi Chalhoub
Ruth Bailey
Ann Falsey
Warren V Kalina
Kevin Cannon
Lisa Usdan
Suchet Patel
Stephen Lockhart
Frank Eder
Bain Butcher
Wayne Harper
David Fitz-Patrick
Curtis Donskey
Mark Mulligan
George Bauer
Peter Winkle
Marcus Lee
Steven Kaster
Steven Cox
√ñzlem T√ºreci
Alexander Murray
Rachael Cavelli
Shane Christensen
Matthew Doust
Jose Cardona
Robert Frenck
Tom Christensen
Edson Moreira
Shelly Senders
Leon Fouche
Douglas Denham
Hector Rodriguez
Murtaza Mussaji
Andrew Gentry
Mark Kutner
Harry Studdard
William C Gruber
Walsh Walsh
Mezgebe Berhe
David Cooper
Thomas Wolf
Robert Falcone
Donald Poretz
Satrajit Roychoudhury
Cecil Farrington
Larry Odekirk
Richard Rupp
Rajesh Davit
James Peterson
Essack Mitha
Rick Whiles
Laura Hammitt
John Earl
Ernest Hendrix
Corey Anderson
Philip R Dormitzer
Robert W Frenck Jr
Stephen Fortmann
Judith Aberg
William Smith
Laura L Hammitt
John L Perez
Kristopher Paolino
Fernando P Polack
Marylyn Addo
Edson D Moreira
William Towner
Gregory Fuller
John Vanchiere
David Fried
Journal: New England Journal of Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: SARS-CoV-2; Covid-19; vaccine; efficacy; safety
Affiliations: From Fundacion INFANT (F.P.P.) and iTrials-Hospital Militar Central (G.P.M.), Buenos Aires; State University of New York, Upstate Medical University, Syracuse (S.J.T.), and Vaccine Research and Development, Pfizer, Pearl River (J.A., A.G., K.A.S., K.K., W.V.K., D.C., P.R.D., K.U.J., W.C.G.) - both in New York; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); Vaccine Research and Development (J.L.P., P.L.) and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Associa√ß√£o Obras Sociais Irm√£ Dulce and Oswaldo Cruz Foundation, Bahia (E.D.M.), and Centro Paulista de Investiga√ß√£o Clinica, S√£o Paulo (C.Z.) - both in Brazil; Global Product Development, Pfizer, Peapack, NJ (S.R.); Cincinnati Children's Hospital, Cincinnati (R.W.F.); Johns Hopkins Bloomberg School of Public Health, Baltimore (L.L.H.); BioNTech, Mainz (√ñT., U.≈û.), and Medizentrum Essen Borbeck, Essen (A.S.) - both in Germany; Tiervlei Trial Centre, Karl Bremer Hospital, Cape Town, South Africa (H.N.); Hacettepe University, Ankara, Turkey (S.√ú.); and Worldwide Safety, Safety Surveillance and Risk Management, Pfizer, Groton, CT (D.B.T.).

Abstract:  Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods: In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 Œºg per dose). BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results: A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.). 

Retracted: No

PubPeer comments:
 It is my understanding that methylated RNA analogs are the backbone of this vaccine. Note that methylated RNA are involved during fetal tissue development among many of the epigenetic alterations that occur. https: pubmed.ncbi.nlm.nih.gov 31036937 https: pubmed.ncbi.nlm.nih.gov 31914637 https: pubmed.ncbi.nlm.nih.gov 31399345 Although the primary targets are specific epitopes on the Covid spike protein, initial vaccination reports from UK perhaps indicate potential reactivity against the methylated mRNA and or the LNPs that make up the vaccine. If it is the former, the T-cell, B-cell repertoire that becomes activated by the vaccine may stay dormant in female subjects, and then become activated and target fetal tissue during a future pregnancy event. I sincerely hope I am 100% wrong! (I am not an immunologist). -Old Timer Biochemist. , 
 Old biochemist, your question is irrelevant to female doctors nurses and subjects beyond reproductive age. BUT it appears relevant to female colleagues and subjects of reproductive age and junior females. Immunogenicity of RNA - let alone methylated RNA - never crossed minds of my team, fellows residents. Let s hope for a quick yes no answer from the trial team. , 
 The NEJM study apparently does not properly control for random fluctuations associated with SARS-CoV-2: https: europepmc.org article PPR PPR241575 , 
 #3 From what I understood, this study by NEJM simulated an epidemic spread SEPARATLY from the placebo and the non-placebo group, which - **if that is the case** - is meaningless :  Then use the log-normal distribution to generate a random sequence of new cases *for each group* . and this is only a preprint ! , 
 The title of the article on this page seems wrong. Here it reads  Scientific Opinion on the safety evaluation of the active substances Sodium carboxy methyl cellulose, bentonite, aluminium potassium sulphate for use in active food contact materials while on the journal  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine . Additionally, there is another pubpeer-entry with the same doi but the correct title https: pubpeer.com publications 25C111CC54FE21B227B35AC3EB198D The Chrome pubpeer extension got me here, while the correctly titled entry I found by using the search function of pubpeer. Can admins fix this issue, perhaps merging these two pages or so? [Moderator: this should now be fixed.] ,