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

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.

• Authors: Paul T Heath, Eva P Galiza, David Neil Baxter, Marta Boffito, Duncan Browne, Fiona Burns, David R Chadwick, Rebecca Clark, Catherine A Cosgrove, James Galloway, Anna L Goodman, Amardeep Heer, Andrew Higham, Shalini Iyengar, Christopher Jeanes, Philip A Kalra, Christina Kyriakidou, Judy M Bradley, Chigomezgo Munthali, Angela M Minassian, Fiona McGill, Patrick Moore, Imrozia Munsoor, Helen Nicholls, Orod Osanlou, Jonathan Packham, Carol H Pretswell, Alberto San Francisco Ramos, Dinesh Saralaya, Ray P Sheridan, Richard Smith, Roy L Soiza, Pauline A Swift, Emma C Thomson, Jeremy Turner, Marianne Elizabeth Viljoen, Louis Fries, Iksung Cho, Irene McKnight, Greg Glenn, E Joy Rivers, Andreana Robertson, Katia Alves, Kathy Smith, Seth Toback
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 76 Issue 3 Pg. 398-407 (02 08 2023) ISSN: 1537-6591 [Electronic] United States
• PMID: 36210481 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Chemical References

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

Topics

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