SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention

Abstract

T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org The Covid-19 epidemic continues to rage, especially in countries that have been unable or unwilling to institute strong public health measures. A return to normality has increasingly come to rely on the success of vaccines to prevent disease and, we hope, limit further spread of infection. However, this hope has been tempered by several unknowns. No existing vaccines have been shown to be effective against infection with any betacoronavirus, the family that includes SARS-CoV-2, which causes Covid-19. SARS, caused by another betacoronavirus, ended on its own before serious efforts at vaccine development were undertaken, and the rather small number of MERS cases has not yet justified the large-scale effort and investment required to determine whether preclinical vaccine candidates are efficacious. In addition, strategies to increase the speed of vaccine development have themselves had only limited testing. A relatively small number of people have received adenovirus-vectored vaccines, and no vaccines based on mRNA technologies have yet been approved. Would these new products be effective and safe? Today we have part of the answer, and it is strongly encouraging. The vaccine BNT162b2 is a modified RNA that encodes a version of the SARS-CoV-2 spike protein containing mutations that lock the protein into a conformation that can induce neutralizing antibody responses. Early clinical trials showed that it could induce both humoral and cellular immunity, although we did not know until now whether these responses would protect against symptomatic infection. Today we know. We are publishing today in the Journal the results of a phase 3, double-blind, randomized, controlled trial of a new RNA vaccine. 1 In this trial, 21,720 participants received BNT162b2 and 21,728 received placebo. Both groups received two injections spaced 21 days apart. Persons with obesity or other coexisting conditions were well represented, and more than 40% of participants were older than 55 years of age. Participants notified trial sites if they had symptoms that were consistent with Covid-19, and they were tested to diagnose infection. They recorded in daily diaries any adverse events they were experiencing. The primary outcomes were safety and the incidence of symptomatic Covid-19 with onset occurring at least a week after the second dose of vaccine or placebo, although all symptomatic infections are reported. The findings in this report include the first 170 cases of Covid-19 detected in the primary population and cover a median of 2 months of safety data. The investigators plan to continue to follow the participants, although once the vaccine becomes freely available, maintaining ran-domization may be a challenge. The results were impressive. In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%). Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55. Adverse events were largely consistent with vaccine reactogenicity, with mostly transient and mild local The New England Journal of Medicine Downloaded from nejm.org on December 15, 2020. For personal use only. No other uses without permission.