Abstract
BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine.
METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.
RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).
CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).
| Original language | English |
|---|---|
| Article number | 2201300 |
| Pages (from-to) | 2084-2096 |
| Number of pages | 13 |
| Journal | The New England Journal of Medicine |
| Volume | 386 |
| Early online date | 4 May 2022 |
| DOIs | |
| Publication status | Published - 2 Jun 2022 |
Bibliographical note
Supported by Medicago with financial assistance from the Canadian Innovation, Science and Economic Development Strategic Innovation Fund. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank all the trial participants; the staff members at each site for their high degree of professionalism in the conduct of the trial; all the employees and contractors at Medicago and GSK for their support; and all the contributors to the GISAID initiative for generating the genetic sequences and metadata on which Figure S1 is based.
Data Availability Statement
Clinical data that support the findings of this studyare available with permission of Medicago from the
corresponding author (Brian J. Ward) or through
communications@medicago.com upon reasonable
request. To protect the privacy of patients and
individuals involved in our studies, Medicago does
not publicly disclose patient-level data
Access to Document
- Hager_etal_NEJM_Efficacy_And_Safety_VoR
From [Publication Title, K.J. Hager, G. Pérez Marc, P. Gobeil, R.S. Diaz, G. Heizer, C. Llapur, A.I. Makarkov, E. Vasconcellos, S. Pillet, F. Riera, P. Saxena, P. Geller Wolff, K. Bhutada, G. Wallace, H. Aazami, C.E. Jones, F.P. Polack, L. Ferrara, J. Atkins, I. Boulay, J. Dhaliwall, N. Charland, M.M.J. Couture, J. Jiang‑Wright, N. Landry, S. Lapointe, A. Lorin, A. Mahmood, L.H. Moulton, E. Pahmer, J. Parent, A. Séguin, L. Tran, T. Breuer, M.-A. Ceregido, M. Koutsoukos, F. Roman, J. Namba, M.-A. D’Aoust, S. Trepanier, Y. Kimura, and B.J. Ward, for the CoVLP Study Team, Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine, Volume No., Page No. Copyright ©2022 Massachusetts Medical Society. Reprinted with permission.