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Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS: We initiated a randomized, placebo-controlled, phase 1–2 trial to evaluate the...

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Autores principales: Keech, Cheryl, Albert, Gary, Cho, Iksung, Robertson, Andreana, Reed, Patricia, Neal, Susan, Plested, Joyce S., Zhu, Mingzhu, Cloney-Clark, Shane, Zhou, Haixia, Smith, Gale, Patel, Nita, Frieman, Matthew B., Haupt, Robert E., Logue, James, McGrath, Marisa, Weston, Stuart, Piedra, Pedro A., Desai, Chinar, Callahan, Kathleen, Lewis, Maggie, Price-Abbott, Patricia, Formica, Neil, Shinde, Vivek, Fries, Louis, Lickliter, Jason D., Griffin, Paul, Wilkinson, Bethanie, Glenn, Gregory M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Massachusetts Medical Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494251/
https://www.ncbi.nlm.nih.gov/pubmed/32877576
http://dx.doi.org/10.1056/NEJMoa2026920
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author Keech, Cheryl
Albert, Gary
Cho, Iksung
Robertson, Andreana
Reed, Patricia
Neal, Susan
Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Zhou, Haixia
Smith, Gale
Patel, Nita
Frieman, Matthew B.
Haupt, Robert E.
Logue, James
McGrath, Marisa
Weston, Stuart
Piedra, Pedro A.
Desai, Chinar
Callahan, Kathleen
Lewis, Maggie
Price-Abbott, Patricia
Formica, Neil
Shinde, Vivek
Fries, Louis
Lickliter, Jason D.
Griffin, Paul
Wilkinson, Bethanie
Glenn, Gregory M.
author_facet Keech, Cheryl
Albert, Gary
Cho, Iksung
Robertson, Andreana
Reed, Patricia
Neal, Susan
Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Zhou, Haixia
Smith, Gale
Patel, Nita
Frieman, Matthew B.
Haupt, Robert E.
Logue, James
McGrath, Marisa
Weston, Stuart
Piedra, Pedro A.
Desai, Chinar
Callahan, Kathleen
Lewis, Maggie
Price-Abbott, Patricia
Formica, Neil
Shinde, Vivek
Fries, Louis
Lickliter, Jason D.
Griffin, Paul
Wilkinson, Bethanie
Glenn, Gregory M.
author_sort Keech, Cheryl
collection PubMed
description BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS: We initiated a randomized, placebo-controlled, phase 1–2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-μg and 25-μg doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti–spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35. RESULTS: After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean, ≤2 days). One participant had mild fever that lasted 1 day. Unsolicited adverse events were mild in most participants; there were no severe adverse events. The addition of adjuvant resulted in enhanced immune responses, was antigen dose–sparing, and induced a T helper 1 (Th1) response. The two-dose 5-μg adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients (8344 and 983, respectively). CONCLUSIONS: At 35 days, NVX-CoV2373 appeared to be safe, and it elicited immune responses that exceeded levels in Covid-19 convalescent serum. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).
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spelling pubmed-74942512020-09-17 Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine Keech, Cheryl Albert, Gary Cho, Iksung Robertson, Andreana Reed, Patricia Neal, Susan Plested, Joyce S. Zhu, Mingzhu Cloney-Clark, Shane Zhou, Haixia Smith, Gale Patel, Nita Frieman, Matthew B. Haupt, Robert E. Logue, James McGrath, Marisa Weston, Stuart Piedra, Pedro A. Desai, Chinar Callahan, Kathleen Lewis, Maggie Price-Abbott, Patricia Formica, Neil Shinde, Vivek Fries, Louis Lickliter, Jason D. Griffin, Paul Wilkinson, Bethanie Glenn, Gregory M. N Engl J Med Original Article BACKGROUND: NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. METHODS: We initiated a randomized, placebo-controlled, phase 1–2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-μg and 25-μg doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti–spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35. RESULTS: After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean, ≤2 days). One participant had mild fever that lasted 1 day. Unsolicited adverse events were mild in most participants; there were no severe adverse events. The addition of adjuvant resulted in enhanced immune responses, was antigen dose–sparing, and induced a T helper 1 (Th1) response. The two-dose 5-μg adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients (8344 and 983, respectively). CONCLUSIONS: At 35 days, NVX-CoV2373 appeared to be safe, and it elicited immune responses that exceeded levels in Covid-19 convalescent serum. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988). Massachusetts Medical Society 2020-09-02 /pmc/articles/PMC7494251/ /pubmed/32877576 http://dx.doi.org/10.1056/NEJMoa2026920 Text en Copyright © 2020 Massachusetts Medical Society. All rights reserved. http://www.nejmgroup.org/legal/terms-of-use.htm This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.
spellingShingle Original Article
Keech, Cheryl
Albert, Gary
Cho, Iksung
Robertson, Andreana
Reed, Patricia
Neal, Susan
Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Zhou, Haixia
Smith, Gale
Patel, Nita
Frieman, Matthew B.
Haupt, Robert E.
Logue, James
McGrath, Marisa
Weston, Stuart
Piedra, Pedro A.
Desai, Chinar
Callahan, Kathleen
Lewis, Maggie
Price-Abbott, Patricia
Formica, Neil
Shinde, Vivek
Fries, Louis
Lickliter, Jason D.
Griffin, Paul
Wilkinson, Bethanie
Glenn, Gregory M.
Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title_full Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title_fullStr Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title_full_unstemmed Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title_short Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
title_sort phase 1–2 trial of a sars-cov-2 recombinant spike protein nanoparticle vaccine
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494251/
https://www.ncbi.nlm.nih.gov/pubmed/32877576
http://dx.doi.org/10.1056/NEJMoa2026920
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