Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months

Abstract

Background: BNT162b2 is a lipid nanoparticle-formulated, nucleoside-modified RNA vaccine encoding a prefusion-stabilized, membrane-anchored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) full-length spike protein. BNT162b2 is highly efficacious against coronavirus disease 2019 (Covid-19) and is currently approved, conditionally approved, or authorized for emergency use worldwide. At the time of initial authorization, data beyond 2 months after vaccination were unavailable.

Methods: 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 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-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 efficacy 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 previous 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 predominant, 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.).

Copyright © 2021 Massachusetts Medical Society.

Figures

Figure 1. Screening, Randomization, and Follow-up.

The diagram represents all enrolled participants 16 years of age or older through the data cutoff date (March 13, 2021). The diagram includes two deaths that occurred after the second dose in human immunodeficiency virus (HIV)–infected participants (one in the BNT162b2 group and one in the placebo group; these deaths were not reported in the Results section of this article because the analysis of HIV-infected participants is being conducted separately). Information on the screening, randomization, and follow-up of the participants 12 to 15 years of age has been reported previously.

Figure 2. Efficacy of BNT162b2 against Covid-19 after Receipt of the First Dose (Blinded Follow-up Period).

The top of the figure shows the cumulative incidence curves for the first occurrence of coronavirus disease 2019 (Covid-19) after receipt of the first dose (efficacy analysis population of participants ≥12 years of age who could be evaluated). Each symbol represents Covid-19 cases starting on a given day, and filled symbols represent severe Covid-19 cases. Because of overlapping dates, some symbols represent more than one case. The inset shows the same data on an enlarged y axis through 21 days. The bottom of the figure shows the time intervals for the first occurrence of Covid-19 in the efficacy analysis population, as well as the surveillance time, which is given as the total time (in 1000 person-years) at risk for the given end point across all participants within each group. The time period for the accrual of Covid-19 cases was from after receipt of the first dose to the end of the surveillance period for the overall row and from the start to the end of the range stated for each time interval. Vaccine efficacy was calculated as 100×(1–IRR), where IRR (incidence rate ratio) is the ratio of the rate (number per 1000 person-years of follow-up) of confirmed cases of Covid-19 in the BNT162b2 group to the corresponding rate in the placebo group. The 95% confidence interval for vaccine efficacy was derived with the use of the Clopper–Pearson method, with adjustment for surveillance time.