Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

Clin Infect Dis. 2023 Feb 8;76(3):398-407. doi: 10.1093/cid/ciac803.

Abstract

Background: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported.

Methods: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.

Results: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.

Conclusions: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated.

Clinical trials registration: EudraCT, 2020-004123-16.

Keywords: COVID-19; SARS-CoV-2; asymptomatic infection; immunogenicity; vaccine efficacy.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral
  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / prevention & control
  • Double-Blind Method
  • Humans
  • Immunogenicity, Vaccine
  • Immunoglobulin G
  • SARS-CoV-2
  • Vaccines, Synthetic / adverse effects

Substances

  • NVX-CoV2373 adjuvated lipid nanoparticle
  • COVID-19 Vaccines
  • Vaccines, Synthetic
  • Immunoglobulin G
  • Antibodies, Viral