Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults

Nature. 2020 Oct;586(7830):589-593. doi: 10.1038/s41586-020-2639-4. Epub 2020 Aug 12.

Abstract

In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19
  • COVID-19 Vaccines
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / therapy
  • Female
  • Humans
  • Immunization, Passive
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Time Factors
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / adverse effects
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2

Supplementary concepts

  • COVID-19 serotherapy

Associated data

  • ClinicalTrials.gov/NCT04368728