The n e w e ng l a n d j o u r na l of m e dic i n e
Original Article
Safety and Efficacy of the BNT162b2 mRNA
Covid-19 Vaccine through 6 Months
S.J. Thomas, E.D. Moreira, Jr., N. Kitchin, J. Absalon, A. Gurtman, S. Lockhart,
J.L. Perez, G. Pérez Marc, F.P. Polack, C. Zerbini, R. Bailey, K.A. Swanson, X. Xu,
S. Roychoudhury, K. Koury, S. Bouguermouh, W.V. Kalina, D. Cooper,
R.W. Frenck, Jr., L.L. Hammitt, Ö. Türeci, H. Nell, A. Schaefer, S. Ünal, Q. Yang,
P. Liberator, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, W.C. Gruber, and
K.U. Jansen, for the C4591001 Clinical Trial Group*
A BS T R AC T
BACKGROUND
BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine The authors’ full names, academic de-
encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syn- grees, and affiliations are listed in the Ap-
pendix. Dr. Dormitzer can be contacted
drome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly at or at
efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, Pfizer, 401 N. Middletown Rd., Pearl River,
conditionally approved, or authorized for emergency use worldwide. At the time of NY 10965.
initial authorization, data beyond 2 months after vaccination were unavailable. *A list of the investigators in the
C4591001 Clinical Trial Group is pro-
METHODS vided in the Supplementary Appendix,
available at NEJM.org.
In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy
trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 This article was published on September 15,
2021, at NEJM.org.
participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of
BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory- DOI: 10.1056/NEJMoa2110345
Copyright © 2021 Massachusetts Medical Society.
confirmed Covid-19 and safety, which were both evaluated through 6 months after
vaccination.
RESULTS
BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few
participants had adverse events leading to withdrawal from the trial. Vaccine ef-
ficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2)
through 6 months of follow-up among the participants without evidence of previ-
ous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in
vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in
populations with diverse ages, sexes, race or ethnic groups, and risk factors for
Covid-19 among participants without evidence of previous infection with SARS-
CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In
South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was pre-
dominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.
CONCLUSIONS
Through 6 months of follow-up and despite a gradual decline in vaccine efficacy,
BNT162b2 had a favorable safety profile and was highly efficacious in preventing
Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
n engl j med nejm.org 1
The New England Journal of Medicine
Downloaded from nejm.org on October 22, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
, The n e w e ng l a n d j o u r na l of m e dic i n e
T
he coronavirus disease 2019 (Covid-19) population (all participants ≥12 years of age)
pandemic continues, with recent estimates reported here.
of more than 187 million cases diagnosed Participants who were healthy or had stable
and more than 4 million deaths.1 Vaccines are chronic medical conditions were eligible. An ac-
currently available by means of full approval, tive immunocompromising condition or recent
conditional marketing approval, and emergency immunosuppressive therapy was an exclusion
use authorization pathways.2-5 BNT162b2 is a criterion. Participants with a history of Covid-19
lipid nanoparticle–formulated,6 nucleoside-mod- were excluded, although evidence of current or
ified RNA7 encoding the severe acute respiratory previous SARS-CoV-2 infection on laboratory test-
syndrome coronavirus 2 (SARS-CoV-2) full-length ing of trial-obtained samples was not an exclu-
spike glycoprotein in a prefusion stabilized con- sion criterion. Trial-related responsibilities and
formation.8 To date, more than 1 billion doses ethical conduct are summarized in the Supplemen-
of BNT162b2 have been distributed. tary Appendix, available with the full text of this
We previously reported safety and efficacy article at NEJM.org. The protocol contains addi-
data obtained through a median of 2 months of tional details of the trial and is available at
postimmunization follow-up from a global NEJM.org. The first draft of the manuscript was
phase 1–2–3 trial of BNT162b2 involving persons written by the fourth author. The authors had
16 years of age or older. Vaccine efficacy against the opportunity to review the data included in
Covid-19 was 95%. BNT162b2 had a favorable this article and confirm the accuracy of the data
safety profile in diverse populations.9 These data presented through the specified data cutoff date.
formed the basis for BNT162b2 emergency or The authors vouch for the accuracy and complete-
conditional authorizations globally.10 Safety, ef- ness of the data and for the fidelity of the trial to
ficacy, and immunogenicity data from partici- the protocol.
pants 12 to 15 years of age in this trial have been
reported.11 Here, we report safety and efficacy Procedures
findings from a prespecified analysis of the The participants were randomly assigned in a
phase 2–3 portion of the trial through approxi- 1:1 ratio to receive two 30-μg intramuscular
mately 6 months of follow-up. These additional injections, 21 days apart, of BNT162b2 (0.3 ml
data contributed to the full approval of BNT162b2 volume per dose) or saline placebo. Random-
in the United States. ization was performed with an interactive Web-
based system. Starting in December 2020, after
BNT162b2 became available under emergency or
Me thods
conditional use authorizations, participants 16
Objectives, Participants, and Oversight years of age or older who became eligible for
This randomized, placebo-controlled, observer- Covid-19 vaccination according to national or
blinded, phase 1–2–3 trial assessed the safety, local recommendations were given the option to
efficacy, and immunogenicity of the BNT162b2 learn their trial assignment. Those who had been
vaccine in adolescents and adults. The current randomly assigned to receive placebo were of-
report of the findings from the phase 2–3 portion fered BNT162b2. After unblinding of the group
of the trial focuses on safety assessments among assignments, participants were followed in an
participants 16 years of age or older and prespeci- open-label trial period.
fied assessments of vaccine efficacy among par-
ticipants 12 years of age or older through 6 months Safety
of follow-up after immunization. Because the en- Safety end points included solicited, prespecified
rollment of participants 12 to 15 years of age local reactions, systemic events, and antipyretic
began on October 15, 2020, 6-month postim- or pain medication use during the first 7 days
munization data are currently unavailable for after receipt of each vaccine or placebo dose,
this age cohort. Shorter-duration safety, immu- which were recorded in an electronic diary; unso-
nogenicity, and efficacy data for participants 12 licited adverse events after receipt of the first dose
to 15 years of age are reported separately11; through 1 month after the second dose; and seri-
however, data for this cohort are included in ous adverse events after receipt of the first dose
the analyses of vaccine efficacy in the overall through 1 and 6 months after the second dose
2 n engl j med nejm.org
The New England Journal of Medicine
Downloaded from nejm.org on October 22, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
Original Article
Safety and Efficacy of the BNT162b2 mRNA
Covid-19 Vaccine through 6 Months
S.J. Thomas, E.D. Moreira, Jr., N. Kitchin, J. Absalon, A. Gurtman, S. Lockhart,
J.L. Perez, G. Pérez Marc, F.P. Polack, C. Zerbini, R. Bailey, K.A. Swanson, X. Xu,
S. Roychoudhury, K. Koury, S. Bouguermouh, W.V. Kalina, D. Cooper,
R.W. Frenck, Jr., L.L. Hammitt, Ö. Türeci, H. Nell, A. Schaefer, S. Ünal, Q. Yang,
P. Liberator, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, W.C. Gruber, and
K.U. Jansen, for the C4591001 Clinical Trial Group*
A BS T R AC T
BACKGROUND
BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine The authors’ full names, academic de-
encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syn- grees, and affiliations are listed in the Ap-
pendix. Dr. Dormitzer can be contacted
drome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly at or at
efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, Pfizer, 401 N. Middletown Rd., Pearl River,
conditionally approved, or authorized for emergency use worldwide. At the time of NY 10965.
initial authorization, data beyond 2 months after vaccination were unavailable. *A list of the investigators in the
C4591001 Clinical Trial Group is pro-
METHODS vided in the Supplementary Appendix,
available at NEJM.org.
In an ongoing, placebo-controlled, observer-blinded, multinational, pivotal efficacy
trial, we randomly assigned 44,165 participants 16 years of age or older and 2264 This article was published on September 15,
2021, at NEJM.org.
participants 12 to 15 years of age to receive two 30-μg doses, at 21 days apart, of
BNT162b2 or placebo. The trial end points were vaccine efficacy against laboratory- DOI: 10.1056/NEJMoa2110345
Copyright © 2021 Massachusetts Medical Society.
confirmed Covid-19 and safety, which were both evaluated through 6 months after
vaccination.
RESULTS
BNT162b2 continued to be safe and have an acceptable adverse-event profile. Few
participants had adverse events leading to withdrawal from the trial. Vaccine ef-
ficacy against Covid-19 was 91.3% (95% confidence interval [CI], 89.0 to 93.2)
through 6 months of follow-up among the participants without evidence of previ-
ous SARS-CoV-2 infection who could be evaluated. There was a gradual decline in
vaccine efficacy. Vaccine efficacy of 86 to 100% was seen across countries and in
populations with diverse ages, sexes, race or ethnic groups, and risk factors for
Covid-19 among participants without evidence of previous infection with SARS-
CoV-2. Vaccine efficacy against severe disease was 96.7% (95% CI, 80.3 to 99.9). In
South Africa, where the SARS-CoV-2 variant of concern B.1.351 (or beta) was pre-
dominant, a vaccine efficacy of 100% (95% CI, 53.5 to 100) was observed.
CONCLUSIONS
Through 6 months of follow-up and despite a gradual decline in vaccine efficacy,
BNT162b2 had a favorable safety profile and was highly efficacious in preventing
Covid-19. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
n engl j med nejm.org 1
The New England Journal of Medicine
Downloaded from nejm.org on October 22, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
, The n e w e ng l a n d j o u r na l of m e dic i n e
T
he coronavirus disease 2019 (Covid-19) population (all participants ≥12 years of age)
pandemic continues, with recent estimates reported here.
of more than 187 million cases diagnosed Participants who were healthy or had stable
and more than 4 million deaths.1 Vaccines are chronic medical conditions were eligible. An ac-
currently available by means of full approval, tive immunocompromising condition or recent
conditional marketing approval, and emergency immunosuppressive therapy was an exclusion
use authorization pathways.2-5 BNT162b2 is a criterion. Participants with a history of Covid-19
lipid nanoparticle–formulated,6 nucleoside-mod- were excluded, although evidence of current or
ified RNA7 encoding the severe acute respiratory previous SARS-CoV-2 infection on laboratory test-
syndrome coronavirus 2 (SARS-CoV-2) full-length ing of trial-obtained samples was not an exclu-
spike glycoprotein in a prefusion stabilized con- sion criterion. Trial-related responsibilities and
formation.8 To date, more than 1 billion doses ethical conduct are summarized in the Supplemen-
of BNT162b2 have been distributed. tary Appendix, available with the full text of this
We previously reported safety and efficacy article at NEJM.org. The protocol contains addi-
data obtained through a median of 2 months of tional details of the trial and is available at
postimmunization follow-up from a global NEJM.org. The first draft of the manuscript was
phase 1–2–3 trial of BNT162b2 involving persons written by the fourth author. The authors had
16 years of age or older. Vaccine efficacy against the opportunity to review the data included in
Covid-19 was 95%. BNT162b2 had a favorable this article and confirm the accuracy of the data
safety profile in diverse populations.9 These data presented through the specified data cutoff date.
formed the basis for BNT162b2 emergency or The authors vouch for the accuracy and complete-
conditional authorizations globally.10 Safety, ef- ness of the data and for the fidelity of the trial to
ficacy, and immunogenicity data from partici- the protocol.
pants 12 to 15 years of age in this trial have been
reported.11 Here, we report safety and efficacy Procedures
findings from a prespecified analysis of the The participants were randomly assigned in a
phase 2–3 portion of the trial through approxi- 1:1 ratio to receive two 30-μg intramuscular
mately 6 months of follow-up. These additional injections, 21 days apart, of BNT162b2 (0.3 ml
data contributed to the full approval of BNT162b2 volume per dose) or saline placebo. Random-
in the United States. ization was performed with an interactive Web-
based system. Starting in December 2020, after
BNT162b2 became available under emergency or
Me thods
conditional use authorizations, participants 16
Objectives, Participants, and Oversight years of age or older who became eligible for
This randomized, placebo-controlled, observer- Covid-19 vaccination according to national or
blinded, phase 1–2–3 trial assessed the safety, local recommendations were given the option to
efficacy, and immunogenicity of the BNT162b2 learn their trial assignment. Those who had been
vaccine in adolescents and adults. The current randomly assigned to receive placebo were of-
report of the findings from the phase 2–3 portion fered BNT162b2. After unblinding of the group
of the trial focuses on safety assessments among assignments, participants were followed in an
participants 16 years of age or older and prespeci- open-label trial period.
fied assessments of vaccine efficacy among par-
ticipants 12 years of age or older through 6 months Safety
of follow-up after immunization. Because the en- Safety end points included solicited, prespecified
rollment of participants 12 to 15 years of age local reactions, systemic events, and antipyretic
began on October 15, 2020, 6-month postim- or pain medication use during the first 7 days
munization data are currently unavailable for after receipt of each vaccine or placebo dose,
this age cohort. Shorter-duration safety, immu- which were recorded in an electronic diary; unso-
nogenicity, and efficacy data for participants 12 licited adverse events after receipt of the first dose
to 15 years of age are reported separately11; through 1 month after the second dose; and seri-
however, data for this cohort are included in ous adverse events after receipt of the first dose
the analyses of vaccine efficacy in the overall through 1 and 6 months after the second dose
2 n engl j med nejm.org
The New England Journal of Medicine
Downloaded from nejm.org on October 22, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
