Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

Karen J Hager; Gonzalo Pérez Marc; Philipe Gobeil; Ricardo S Diaz; Gretchen Heizer; Conrado Llapur; Alexander I Makarkov; Eduardo Vasconcellos; Stéphane Pillet; Fernando Riera; Pooja Saxena; Priscila Geller Wolff; Kapil Bhutada; Garry Wallace; Hessam Aazami; Christine E Jones; Fernando P Polack; Luciana Ferrara; Judith Atkins; Iohann Boulay; Jiwanjeet Dhaliwall; Nathalie Charland; Manon M J Couture; Julia Jiang-Wright; Nathalie Landry; Sophie Lapointe; Aurélien Lorin; Asif Mahmood; Lawrence H Moulton; Emily Pahmer; Julie Parent; Annie Séguin; Luan Tran; Thomas Breuer; Maria-Angeles Ceregido; Marguerite Koutsoukos; François Roman; Junya Namba; Marc-André D'Aoust; Sonia Trepanier; Yosuke Kimura; Brian J Ward; CoVLP Study Team

doi:10.1056/NEJMoa2201300

Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

Karen J Hager, Gonzalo Pérez Marc, Philipe Gobeil, Ricardo S Diaz, Gretchen Heizer, Conrado Llapur, Alexander I Makarkov, Eduardo Vasconcellos, Stéphane Pillet, Fernando Riera, Pooja Saxena, Priscila Geller Wolff, Kapil Bhutada, Garry Wallace, Hessam Aazami, Christine E Jones, Fernando P Polack, Luciana Ferrara, Judith Atkins, Iohann BoulayJiwanjeet Dhaliwall, Nathalie Charland, Manon M J Couture, Julia Jiang-Wright, Nathalie Landry, Sophie Lapointe, Aurélien Lorin, Asif Mahmood, Lawrence H Moulton, Emily Pahmer, Julie Parent, Annie Séguin, Luan Tran, Thomas Breuer, Maria-Angeles Ceregido, Marguerite Koutsoukos, François Roman, Junya Namba, Marc-André D'Aoust, Sonia Trepanier, Yosuke Kimura, Brian J Ward, CoVLP Study Team

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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
Number of pages	13
Journal	The New England Journal of Medicine
Early online date	4 May 2022
DOIs	https://doi.org/10.1056/NEJMoa2201300
Publication status	E-pub ahead of print - 4 May 2022

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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.
Final published version, 1.05 MBLicence: Other

Cite this

Hager, K. J., Pérez Marc, G., Gobeil, P., Diaz, R. S., Heizer, G., Llapur, C., Makarkov, A. I., Vasconcellos, E., Pillet, S., Riera, F., Saxena, P., Geller Wolff, P., Bhutada, K., Wallace, G., Aazami, H., Jones, C. E., Polack, F. P., Ferrara, L., Atkins, J., ... CoVLP Study Team (2022). Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2201300

Hager, KJ, Pérez Marc, G, Gobeil, P, Diaz, RS, Heizer, G, Llapur, C, Makarkov, AI, Vasconcellos, E, Pillet, S, Riera, F, Saxena, P, Geller Wolff, P, Bhutada, K, Wallace, G, Aazami, H, Jones, CE, Polack, FP, Ferrara, L, Atkins, J, Boulay, I, Dhaliwall, J, Charland, N, Couture, MMJ, Jiang-Wright, J, Landry, N, Lapointe, S, Lorin, A, Mahmood, A, Moulton, LH, Pahmer, E, Parent, J, Séguin, A, Tran, L, Breuer, T, Ceregido, M-A, Koutsoukos, M, Roman, F, Namba, J, D'Aoust, M-A, Trepanier, S, Kimura, Y, Ward, BJ & CoVLP Study Team 2022, 'Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine', The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2201300

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title = "Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine",

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.).",

author = "Hager, {Karen J} and {P{\'e}rez Marc}, Gonzalo and Philipe Gobeil and Diaz, {Ricardo S} and Gretchen Heizer and Conrado Llapur and Makarkov, {Alexander I} and Eduardo Vasconcellos and St{\'e}phane Pillet and Fernando Riera and Pooja Saxena and {Geller Wolff}, Priscila and Kapil Bhutada and Garry Wallace and Hessam Aazami and Jones, {Christine E} and Polack, {Fernando P} and Luciana Ferrara and Judith Atkins and Iohann Boulay and Jiwanjeet Dhaliwall and Nathalie Charland and Couture, {Manon M J} and Julia Jiang-Wright and Nathalie Landry and Sophie Lapointe and Aur{\'e}lien Lorin and Asif Mahmood and Moulton, {Lawrence H} and Emily Pahmer and Julie Parent and Annie S{\'e}guin and Luan Tran and Thomas Breuer and Maria-Angeles Ceregido and Marguerite Koutsoukos and Fran{\c c}ois Roman and Junya Namba and Marc-Andr{\'e} D'Aoust and Sonia Trepanier and Yosuke Kimura and Ward, {Brian J} and {CoVLP Study Team} and Roy Soiza",

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.",

year = "2022",

month = may,

day = "4",

doi = "10.1056/NEJMoa2201300",

language = "English",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

}

TY - JOUR

T1 - Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

AU - Hager, Karen J

AU - Pérez Marc, Gonzalo

AU - Gobeil, Philipe

AU - Diaz, Ricardo S

AU - Heizer, Gretchen

AU - Llapur, Conrado

AU - Makarkov, Alexander I

AU - Vasconcellos, Eduardo

AU - Pillet, Stéphane

AU - Riera, Fernando

AU - Saxena, Pooja

AU - Geller Wolff, Priscila

AU - Bhutada, Kapil

AU - Wallace, Garry

AU - Aazami, Hessam

AU - Jones, Christine E

AU - Polack, Fernando P

AU - Ferrara, Luciana

AU - Atkins, Judith

AU - Boulay, Iohann

AU - Dhaliwall, Jiwanjeet

AU - Charland, Nathalie

AU - Couture, Manon M J

AU - Jiang-Wright, Julia

AU - Landry, Nathalie

AU - Lapointe, Sophie

AU - Lorin, Aurélien

AU - Mahmood, Asif

AU - Moulton, Lawrence H

AU - Pahmer, Emily

AU - Parent, Julie

AU - Séguin, Annie

AU - Tran, Luan

AU - Breuer, Thomas

AU - Ceregido, Maria-Angeles

AU - Koutsoukos, Marguerite

AU - Roman, François

AU - Namba, Junya

AU - D'Aoust, Marc-André

AU - Trepanier, Sonia

AU - Kimura, Yosuke

AU - Ward, Brian J

AU - CoVLP Study Team

AU - Soiza, Roy

N1 - 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.

PY - 2022/5/4

Y1 - 2022/5/4

N2 - 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.).

AB - 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.).

U2 - 10.1056/NEJMoa2201300

DO - 10.1056/NEJMoa2201300

M3 - Article

C2 - 35507508

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

ER -

Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine

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