Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: randomised, active-controlled, observer-blinded, phase 3 trial (preprint)

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) up to 2 weeks after the second dose, and safety data up to a median of 2.5 months follow-up. Methods: Randomised, active-controlled, observer-blinded, multinational study: Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination, n=1956) randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety); Cohort 2 (regardless of baseline serostatus; n=2080) randomised 5:1 (safety). Primary objectives: demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; [≥]4-fold rise from baseline) of GBP510/AS03 versus ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity. Findings: At 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03 / ChAdOx1-S) was 2.93 (95% CI 2.63 - 3.27), demonstrating superiority (95% CI lower limit >1). The between-group SCR difference of 10.76% (95% CI 7.68 - 14.32) satisfied the non-inferiority criterion (95% CI lower limit >5%).The proportion of subjects with adverse events (AEs) after any vaccination was higher with GBP510/AS03 versus ChAdOx1-S for solicited local AEs (56.69% vs 49.20%), but was similar for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.27% vs 14.56%). No safety concerns were identified during follow-up for a median 2.5-months after the second vaccination. Interpretation: GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: a phase 1/2, randomized, placebo-controlled, observer-blinded trial (preprint)

Background - Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods - We conducted a randomized, placebo-controlled, observer-blinded, phase 1/2 trial to evaluate the safety and immunogenicity of GBP510 (2-doses at a-28-day interval) adjuvanted with or without AS03 in adults aged 19-85 years. The main outcomes included solicited and unsolicited adverse events; anti-SARS-CoV-2 RBD IgG antibody and neutralizing antibody responses; T-cell immune responses. Findings Of 328 participants underwent randomization, 327 participants received at least 1 dose of study. Each received either 10 {micro}g GBP510 adjuvanted with AS03 (n = 101), 10 {micro}g unadjuvanted GBP510 (n = 10), 25 {micro}g GBP510 adjuvanted with AS03 (n = 104), 25 {micro}g unadjuvanted GBP510 (n = 51), or placebo (n = 61). Most solicited adverse events were mild-to-moderate in severity and transient. Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic adverse events. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163.6/2599.2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 {micro}g/25 {micro}g) by 14 days after the second dose. Two-dose vaccination of 10 {micro}g or 25 {micro}g GBP510 adjuvanted with AS03 induced high titers of neutralizing antibody via pseudovirus (1369.0/1431.5 IU/mL) and wild-type virus (949.8/861.0 IU/mL) assays. Interpretation - GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently evaluated in Phase 3