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

Type Journal Article Author Cheryl Keech Author Gary Albert Author Iksung Cho Author Andreana Robertson Author Patricia Reed Author Susan Neal Author Joyce S. Plested Author Mingzhu Zhu Author Shane Cloney-Clark Author Haixia Zhou Author Gale Smith Author Nita Patel Author Matthew B. Frieman Author Robert E. Haupt Author James Logue Author Marisa McGrath Author Stuart Weston Author Pedro A. Piedra Author Chinar Desai Author Kathleen Callahan Author Maggie Lewis Author Patricia Price-Abbott Author Neil Formica Author Vivek Shinde Author Louis Fries Author Jason D. Lickliter Author Paul Griffin Author Bethanie Wilkinson Author Gregory M. Glenn URL https://www.nejm.org/doi/10.1056/NEJMoa2026920 Rights Copyright © 2020 Massachusetts Medical Society. All rights reserved. Publication New England Journal of Medicine Date 10/12/2020 Loc. in Archive world Extra Publisher: Massachusetts Medical Society DOI 10.1056/NEJMoa2026920 Library Catalog www.nejm.org Language en Abstract Original Article from The New England Journal of Medicine — 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 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).