Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

作者：Edward E. Walsh, Robert W. Frenck, Ann Regina Falsey, Nicholas R.E. Kitchin, Judith Absalon, Alejandra Gurtman, Stephen P. Lockhart, Kathleen Maletic Neuzil, Mark J. Mulligan, Ruth E. Bailey, Kena A. Swanson, Ping Li, Kenneth J. Koury, Warren V. Kalina, David A. Cooper, Camila R. Fontes-Garfias, Pei‐Yong Shi, Özlem Türeci, Kristin R. Tompkins, Kirsten E. Lyke, Vanessa Raabe, Philip R. Dormitzer, Kathrin U. Jansen, Uğur Şahin, William C. Gruber · 发表于：New England Journal of Medicine · 年份：2020 · DOI：10.1056/nejmoa2027906 · 被引用次数：2745 · 研究领域：SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies、COVID-19 Clinical Research Studies

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...