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Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine.
N Engl J Med. 2020 Sep 02 [Online ahead of print]NEJM

Abstract

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).

Authors+Show Affiliations

From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.From Novavax, Gaithersburg, MD (C.K., G.A., I.C., A.R., P.R., S.N., J.S.P., M.Z., S.C.-C., H.Z., G.S., N.P., C.D., K.C., M.L., P.P.-A., N.F., V.S., L.F., B.W., G.M.G.), and the University of Maryland School of Medicine, Baltimore (M.B.F., R.E.H., J.L., M.M.G., S.W.); Baylor College of Medicine, Houston (P.A.P.); and Nucleus Network, Melbourne, VIC (J.D.L.), and Q-Pharm, Herston, QLD (P.G.) - both in Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32877576

Citation

Keech, Cheryl, et al. "Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine." The New England Journal of Medicine, 2020.
Keech C, Albert G, Cho I, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020.
Keech, C., Albert, G., Cho, I., Robertson, A., Reed, P., Neal, S., Plested, J. S., Zhu, M., Cloney-Clark, S., Zhou, H., Smith, G., Patel, N., Frieman, M. B., Haupt, R. E., Logue, J., McGrath, M., Weston, S., Piedra, P. A., Desai, C., ... Glenn, G. M. (2020). Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2026920
Keech C, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020 Sep 2; PubMed PMID: 32877576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. AU - Keech,Cheryl, AU - Albert,Gary, AU - Cho,Iksung, AU - Robertson,Andreana, AU - Reed,Patricia, AU - Neal,Susan, AU - Plested,Joyce S, AU - Zhu,Mingzhu, AU - Cloney-Clark,Shane, AU - Zhou,Haixia, AU - Smith,Gale, AU - Patel,Nita, AU - Frieman,Matthew B, AU - Haupt,Robert E, AU - Logue,James, AU - McGrath,Marisa, AU - Weston,Stuart, AU - Piedra,Pedro A, AU - Desai,Chinar, AU - Callahan,Kathleen, AU - Lewis,Maggie, AU - Price-Abbott,Patricia, AU - Formica,Neil, AU - Shinde,Vivek, AU - Fries,Louis, AU - Lickliter,Jason D, AU - Griffin,Paul, AU - Wilkinson,Bethanie, AU - Glenn,Gregory M, Y1 - 2020/09/02/ PY - 2020/9/3/entrez PY - 2020/9/3/pubmed PY - 2020/9/3/medline JF - The New England journal of medicine JO - N. Engl. J. Med. N2 - 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). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/32877576/full_citation L2 - https://www.nejm.org/doi/10.1056/NEJMoa2026920?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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