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

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

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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).

Subfields: Infectious Diseases, Molecular Biology

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “…potent neutralizing activity obtained by immunization with prefusion-stabilized (S-2P) ectodomain (Mandolesi et al., 2020) and full-length trimers (Keech et al., 2020) formulated with powerful adjuvants provide promising data on the immunogenicity of vaccine candidates based on recombinant S…”
COVID-19 vaccines (2021, background): “There are currently 33 SARS-CoV-2 protein subunit candidate vaccines in clinical development [5], with at least one that has been shown in phase III clinical trials to induce high titers of neutralizing antibodies [17].”
Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial (2020, positive): “26 An adjuvanted nanoparticle vaccine has been shown to induce spike-specific CD4 T-cell cytokine responses with a predominantly Th1 profile, 15 as has an mRNA vaccine in small numbers of adults aged 56–70 years and 71 years and older.”
Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, positive): “Multiple candidate vaccines had similar immunogenicity profiles to the COVID-19 RNA vaccines in humans, with equivalent or better neutralizing antibody titers or CD4 T cell responses (Folegatti et al., 2020; Jackson et al., 2020; Keech et al., 2020; Zhu et al., 2020).”