First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine

By C. Keech, G. Glenn, G. Albert, I. Cho, A. Robertson, P. Reed, S. Neal, J. Plested, Mingzhu Zhu, S. Cloney-Clark and 19 more. 2020

35 citations recorded by the source corpus.

Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean [≥] 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5g NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

Subfields: Infectious Diseases, Molecular Biology

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In Infectious Diseases

1. D. Veesler
2. A. Walls
3. Ralph S. Baric

In Molecular Biology

1. M. Navarro
2. Neil P. King
3. Kelly K. Lee
4. Ralph S. Baric
5. M. Guttman
6. Lauren P. Carter
7. A. Walls
8. D. Veesler

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, background): “This metric has been identified as a potentially important indicator of vaccine safety, as high levels of binding yet non-neutralizing or weakly neutralizing Abs may contribute to vaccine-associated enhancement of respiratory disease (Graham, 2020; Kim et al., 1969; Polack et al., 2002).”