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Safety and Efficacy of the Two Doses Conjugated Protein-Based SOBERANA-02 COVID-19 Vaccine and of a Heterologous Three-Dose Combination with SOBERANA-PLUS: Double-Blind, Randomised, Placebo-Controlled Phase 3 Clinical Trial
24 Pages Posted: 27 Jul 2022More...
Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralizing IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralizing antibodies.
Methods: From March 8th to September 30th, 2021 we conducted in Havana, Cuba a multicentre randomized, double-blind, placebo-controlled, phase-3 trial evaluating two doses of SOBERANA-02 and a heterologous scheme with one dose SOBERANA-Plus added to it. Participants 19–80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 occurring at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose.
Finding: We included 44·031 participants in a context of Beta VOC predominance, with this variant being gradually replaced by Delta near the trial end. Vaccine efficacy in the heterologous combination was 92·0% (95%CI 80·4–96·7) against symptomatic and 100% against severe COVID-19. Two doses of SOBERANA-02 was 69·7% (95%CI 56·5-78·9) and 74·9% (95%CI 33·7-90·5) efficacious to protect against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe AEs was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient.
Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC dominance and that they constitute an attractive, feasible option for low- and middle-income countries, where besides financial constraints ease of vaccine storage and distribution is of concern.
Trial Registration Details: (Clinical Trials IFV/COR/09 number, RPCEC00000354).
Funding Information: This study received funds from Finlay Vaccine Institute and National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020–20). of Ministry of Science, Technology and the Environment (Contract Project-2020-20) in Cuba.
Declaration of Interests: None to declare.
Ethics Approval Statement: The trial was sponsored by the Finlay Vaccine Institute. A central Research Ethics Committee was appointed ad hoc by the Cuban Ministry of Public Health. . It approved the protocol. and the informed consent forms. In the event of a medical problem requiring unmasking, approval by the principal investigator was planned for. All principles of the Helsinki Declaration and the International Council for Harmonization guidelines were adhered to. Full details on procedures are provided in the protocol. The National Clinical Trials Coordinating Centre (CENCEC) monitored the trial for protocol adherence and observance of Good Clinical Practice, and oversaw data accuracy. An Independent Safety Data Monitoring Board (ISDMB) continuously supervised safety and conducted interim analysis. The ISDMB had access to the case files, confirmed severe cases of COVID-19 illness, and assessed whether any deaths were SARS CoV-2-related.
Keywords: conjugate-vaccine, SARS-COV-2, COVID-19 Vaccine, heterologous scheme, RBD-subunit vaccine, vaccine efficacy
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