| Autor: |
Joon Young Song, Won Suk Choi, Jung Yeon Heo, Eun Jin Kim, Jin Soo Lee, Dong Sik Jung, Shin-Woo Kim, Kyung-Hwa Park, Joong Sik Eom, Su Jin Jeong, Jacob Lee, Ki Tae Kwon, Hee Jung Choi, Jang Wook Sohn, Young Keun Kim, Byung Wook Yoo, In-Jin Jang, Maria R. Capeding, François Roman, Thomas Breuer, Piotr Wysocki, Lauren Carter, Sushant Sahastrabuddhe, Manki Song, Naveena D’Cor, Hun Kim, Ji Hwa Ryu, Su Jeen Lee, Yong Wook Park, Hee Jin Cheong |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.01.31.23284895 |
| Popis: |
BackgroundGBP510 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.MethodsRandomised, 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.FindingsAt 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.InterpretationGBP510/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.FundingThis 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.RESEARCH IN CONTEXTEvidence before this studyImmunobridging has been proposed as an approach for assessing new COVID-19 vaccines by comparing the immunogenicity of candidate vaccines with an active comparator with demonstrated clinical efficacy. We searched PubMed up to 26 October 2022 for immunobridging clinical trials comparing a candidate vaccine with an approved vaccine, using the terms “immunobridging”, “SARS-CoV-2”, “COVID-19”, and “vaccine”. A phase 2/3 study showed that the ChAdOx1 vaccine, manufactured by the Serum Institute of India after technology transfer from Oxford University/AstraZeneca, had a non-inferior immune response compared to the original ChAdOx1 (AZD1222) vaccine. A post hoc analysis of phase 2 data found that MVC-COV1901 vaccine (a protein subunit vaccine developed by Medigen Vaccine Biologics Corporation, Taiwan) was non-inferior to ChAdOx1 (AZD1222) with respect to neutralising antibody titres. A phase 3 study found that VLA2001 (an adjuvanted, inactivated whole-virus vaccine developed by Valneva, Austria) was superior to ChAdOx1 with respect to neutralising antibody titres and non-inferior with respect to seroconversion rates.Added value of this studyThis is the first study comparing the immunogenicity of recombinant SARS-CoV-2 protein nanoparticle vaccine GBP510 adjuvanted with AS03 versus ChAdOx1-S. Interim analysis found that two-dose vaccination with GBP510/AS03 induced stronger neutralising antibody immune responses compared with ChAdOx1-S against the ancestral D614G strain at 2 weeks after the second dose. GBP510/AS03 had an acceptable safety profile during a median 2.5 months of follow-up.Implications of the available evidenceThis interim analysis suggests that GBP510/AS03 induces strong neutralising antibody responses against SARS-CoV-2 ancestral strain and has an acceptable safety profile. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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