Immunogenicity of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in SARS-CoV-2-naïve and exposed individuals in a phase 2/3, double-blind, randomized study.

BACKGROUND

We evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a pre-fusion trimeric form of the SARS-CoV-2 spike (S)-protein adjuvanted with CpG-1018/alum.

METHODS

The phase 2/3, double-blind, randomized SPECTRA trial was conducted in five countries in participants aged ≥ 18 years, either SARS-CoV-2-naïve or previously exposed. Participants were randomly assigned to receive two doses of SCB-2019 or placebo administered intramuscularly 21 days apart. In the phase 2 part of the study, on days 1, 22, and 36, neutralizing antibodies were measured by pseudovirus and wild-type virus neutralization assays to SARS-CoV-2 prototype and variants, and ACE2-receptor-binding antibodies and SCB-2019-binding antibodies were measured by ELISA. Cell-mediated immunity was measured by intracellular cytokine staining via flow cytometry.

RESULTS

1601 individuals were enrolled between 24 March and 13 September 2021 and received at least one vaccine dose. Immunogenicity analysis was conducted in a phase 2 subset of 691 participants, including 428 SARS-CoV-2-naïve (381 vaccine and 47 placebo recipients) and 263 SARS-CoV-2-exposed (235 vaccine and 28 placebo recipients). In SARS-CoV-2-naïve participants, GMTs of neutralizing antibodies against prototype virus increased 2 weeks post-second dose (day 36) compared to baseline (224 vs 12.7 IU/mL). Seroconversion rate was 82.5 %. In SARS-CoV-2-exposed participants, one SCB-2019 dose increased GMT of neutralizing antibodies by 48.3-fold (1276.1 IU/mL on day 22) compared to baseline. Seroconversion rate was 92.4 %. Increase was marginal post-second dose. SCB-2019 also showed cross-neutralization capability against nine variants, including Omicron, in SARS-CoV-2-exposed participants at day 36. SCB-2019 stimulated Th1-biased cell-mediated immunity to the S-protein in both naïve and exposed participants. The vaccine was well tolerated, no safety concerns were raised from the study.

CONCLUSIONS

A single dose of SCB-2019 was immunogenic in SARS-CoV-2-exposed individuals, whereas two doses were required to induce immune response in SARS-CoV-2-naïve individuals. SCB-2019 elicited a cross-neutralizing response against emergent SARS-CoV-2 variants at antibody levels associated with clinical protection, underlining its potential as a booster.

CLINICALTRIALS

gov: NCT04672395; EudraCT: 2020-004272-17.

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MH received financial support from Clover Biopharmaceuticals, grants from the European Union, the Belgian Health Care Knowledge Centre, and Université Libre de Bruxelles, travel fees from Gilead and Pfizer, financial support from INSMED, is involved in the Belgian Society of Infectious Diseases and Clinical Microbiology, the working group on Belgian COVID-19 therapeutic guidelines, and the Belgian Task Force on therapeutics for COVID-19. GS served as a Scientific Advisory Board Member and received consulting fees from Clover Biopharmaceuticals, AdVaccine, CanSino, Everest Medicines, Valneva, Vaxart, Affinivax, Genocea, and Vaxxess. DA received consulting fees from Clover Biopharmaceuticals, Vaxxinity, Everest Medicines, Senda, served as a Scientific Advisory Board Member for Clover Biopharmaceuticals, Vaxxinity, Senda, Everest Medicines, and Inventprise, and served as a board member for Clover Biopharmaceuticals and Inventprise. RC received funding from the Bill & Melinda Gates Foundation, consulting fees from Icosavax, Hillevax, honoraria from AstraZeneca, served as a board member for Clover Biopharmaceuticals, Curevac, IVI, Inventprise, and owns stocks in Icosavax, Hillevax, Curevac, Novartis, Roche, GSK, and Clover Biopharmaceuticals. EB had contracts with Clover Biopharmaceuticals, Astra-Zeneca, Janssen, GSK, Merck, and Moderna. ERA, JCC, LFBF, and MEBM declare that they have no competing financial interests. BH, HHH, HQ, and HLC are employees of Clover Biopharmaceuticals. CB is an employee of Clover Biopharmaceuticals owns stocks in Clover Biopharmaceuticals, GSK, and Sanofi. PL and IS are employees of Clover Biopharmaceuticals and own stocks in the company.