Edward E Walsh, et al.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease,coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide.Multiple vaccine candidates are under development, but no vaccine is currently available.Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States.

Methods: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States,we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation.The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome.Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg).In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose.

Results: A total of 195 participants underwent randomization.In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo.BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults.In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples.

Conclusions: The safety and immunogenicity data from this U.S.phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation.(Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).