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

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

doi:10.1093/cid/ciac803

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

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 MinassianFiona 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

Applied Medicine

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Abstract

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against 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 two 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 seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.

RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) 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% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (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 two-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 dose may be indicated.

Original language	English
Pages (from-to)	398-407
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	76
Issue number	3
Early online date	10 Oct 2022
DOIs	https://doi.org/10.1093/cid/ciac803
Publication status	Published - 1 Feb 2023

Keywords

CoVID-19
Immunogenicity
Asymptomatic Infections
SARS-CoV-2
Vaccine efficacy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Heath, P. T., Galiza, E. P., Baxter, D. N., Boffito, M., Browne, D., Burns, F., Chadwick, D. R., Clark, R., Cosgrove, C. A., Galloway, J., Goodman, A. L., Heer, A., Higham, A., Iyengar, S., Jeanes, C., Kalra, P. A., Kyriakidou, C., Bradley, J. M., Munthali, C., ... Toback, S. (2023). Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial. Clinical Infectious Diseases, 76(3), 398-407. https://doi.org/10.1093/cid/ciac803

Heath, PT, Galiza, EP, Baxter, DN, Boffito, M, Browne, D, Burns, F, Chadwick, DR, Clark, R, Cosgrove, CA, Galloway, J, Goodman, AL, Heer, A, Higham, A, Iyengar, S, Jeanes, C, Kalra, PA, Kyriakidou, C, Bradley, JM, Munthali, C, Minassian, AM, McGill, F, Moore, P, Munsoor, I, Nicholls, H, Osanlou, O, Packham, J, Pretswell, CH, Francisco Ramos, AS, Saralaya, D, Sheridan, RP, Smith, R, Soiza, RL, Swift, PA, Thomson, EC, Turner, J, Viljoen, ME, Fries, L, Cho, I, McKnight, I, Glenn, G, Rivers, EJ, Robertson, A, Alves, K, Smith, K & Toback, S 2023, 'Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial', Clinical Infectious Diseases, vol. 76, no. 3, pp. 398-407. https://doi.org/10.1093/cid/ciac803

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title = "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 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 two 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 seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) 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% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (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 two-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 dose may be indicated.",

keywords = "CoVID-19, Immunogenicity, Asymptomatic Infections, SARS-CoV-2, Vaccine efficacy",

author = "Heath, {Paul T} and Galiza, {Eva P} and Baxter, {David Neil} and Marta Boffito and Duncan Browne and Fiona Burns and Chadwick, {David R} and Rebecca Clark and Cosgrove, {Catherine A} and James Galloway and Goodman, {Anna L} and Amardeep Heer and Andrew Higham and Shalini Iyengar and Christopher Jeanes and Kalra, {Philip A} and Christina Kyriakidou and Bradley, {Judy M} and Chigomezgo Munthali and Minassian, {Angela M} and Fiona McGill and Patrick Moore and Imrozia Munsoor and Helen Nicholls and Orod Osanlou and Jonathan Packham and Pretswell, {Carol H} and {Francisco Ramos}, {Alberto San} and Dinesh Saralaya and Sheridan, {Ray P} and Richard Smith and Soiza, {Roy L} and Swift, {Pauline A} and Thomson, {Emma C} and Jeremy Turner and Viljoen, {Marianne Elizabeth} and Louis Fries and Iksung Cho and Irene McKnight and Greg Glenn and Rivers, {E Joy} and Andreana Robertson and Katia Alves and Kathy Smith and Seth Toback",

note = "Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of Novavax",

year = "2023",

month = feb,

day = "1",

doi = "10.1093/cid/ciac803",

language = "English",

volume = "76",

pages = "398--407",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

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TY - JOUR

T1 - Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial

AU - Heath, Paul T

AU - Galiza, Eva P

AU - Baxter, David Neil

AU - Boffito, Marta

AU - Browne, Duncan

AU - Burns, Fiona

AU - Chadwick, David R

AU - Clark, Rebecca

AU - Cosgrove, Catherine A

AU - Galloway, James

AU - Goodman, Anna L

AU - Heer, Amardeep

AU - Higham, Andrew

AU - Iyengar, Shalini

AU - Jeanes, Christopher

AU - Kalra, Philip A

AU - Kyriakidou, Christina

AU - Bradley, Judy M

AU - Munthali, Chigomezgo

AU - Minassian, Angela M

AU - McGill, Fiona

AU - Moore, Patrick

AU - Munsoor, Imrozia

AU - Nicholls, Helen

AU - Osanlou, Orod

AU - Packham, Jonathan

AU - Pretswell, Carol H

AU - Francisco Ramos, Alberto San

AU - Saralaya, Dinesh

AU - Sheridan, Ray P

AU - Smith, Richard

AU - Soiza, Roy L

AU - Swift, Pauline A

AU - Thomson, Emma C

AU - Turner, Jeremy

AU - Viljoen, Marianne Elizabeth

AU - Fries, Louis

AU - Cho, Iksung

AU - McKnight, Irene

AU - Glenn, Greg

AU - Rivers, E Joy

AU - Robertson, Andreana

AU - Alves, Katia

AU - Smith, Kathy

AU - Toback, Seth

N1 - Acknowledgements The study and article were funded by Novavax. We would like to thank all the study participants for their commitment to this study. We also acknowledge the investigators and their study teams for their hard work and dedication. In addition, we would like to thank the National Institute for Health Research, representatives from the Department of Health and Social Care laboratories and NHS Digital and the members of the UK Vaccine Task Force. Editorial support was provided by Kelly Cameron of Ashfield MedComms, an Inizio company Funding This work was funded by Novavax, and the sponsor had primary responsibility for study design, study vaccines, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission. LF reports a position as a prior full-time employee, now contractor to Novavax re-imbursed hourly for work performed on this study and in analyses and drafting this report. IC reports providing medical writing support for this work as an employee of Novavax

PY - 2023/2/1

Y1 - 2023/2/1

N2 - BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against 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 two 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 seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) 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% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (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 two-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 dose may be indicated.

AB - BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against 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 two 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 seroconverted to immunoglobulin G (IgG) against the nucleocapsid protein and did not meet criteria for symptomatic COVID-19 were classified as having asymptomatic disease. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.RESULTS: Of 15185 participants, 13989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5 months) 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% CI: 73.3-88.8). Vaccine efficacy was 100% (17.9-100.0) against severe disease and 76.3% (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 two-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 dose may be indicated.

KW - CoVID-19

KW - Immunogenicity

KW - Asymptomatic Infections

KW - SARS-CoV-2

KW - Vaccine efficacy

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U2 - 10.1093/cid/ciac803

DO - 10.1093/cid/ciac803

M3 - Article

C2 - 36210481

VL - 76

SP - 398

EP - 407

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 3

ER -

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

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UN SDGs

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