• Citer

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

par Buntinx, Erik;Brochado, Leonardo;Borja-Tabora, Charissa;Yu, Charles Y.;Alberto, Edison R;Montellano, May Emmeline;Carlos, Josefina C.;Toloza, Leonardo Bautista;Hites, Maya ;Siber, George;Clemens, Ralf;Ambrosino, Donna;Qin, Haijing;Chen, Hui Ling;Han, Htay Htay;Hu, Branda;Li, Ping;Baccarini, Carmen;Smolenov, Igor
Référence Vaccine
Publication Publié, 2023-02-01

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

Background: We evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a prefusion 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-mediatedimmunity 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 crossneutralization 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