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Safety and Immunogenicity of Anti-SARS-CoV-2 Conjugate Vaccine SOBERANA 02: Phase IIb Clinical Trial

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4023682

1556-5068

María Eugenia-Toledo-Romaní, Mayra García Carmenate, Leslyhana Verdecia-Sánchez, Suzel Pérez-Rodríguez, Meiby Rodríguez-González, Carmen Valenzuela‐Silva, Beatriz Paredes-Moreno, Belinda Sánchez-Ramírez, Raúl González-Mugica, Tays Hernández-García, Ivette Orosa-Vázquez, Marianniz Díaz-Hernández, María Teresa Pérez-Guevara, Juliet Enríquez-Puertas, Enrique Noa-Romero, Ariel Palenzuela-Díaz, Gerardo Baró-Román, Ivis Mendoza-Hernández, Yaima Muñoz, Yanet Gómez-Maceo, Bertha Leysi Santos Vega, Sonsire Fernández-Castillo, Yanet Climent-Ruíz, Laura Rodríguez-Noda, Darielys Santana-Mederos, Yanelda García-Vega, Guang Wu-Chen, Delaram Doroud, Alireza Biglari, Tammy Boggiano-Ayo, Yury Valdés-Balbín, Daniel G. Rivera, Dagmar García-Rivera, Vicente Vérez-Bencomo, SOBERANA Research Group,

COVID-19 Clinical Research Studies

Background: SOBERANA 02 have been evaluated in phase I and IIa studies comparing homologous vs. heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults.Method: Phase IIb was a parallel, multicenter, adaptive, double blind, randomized and placebo-controlled trial. Subjects (N=810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredient of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD IgG concentration. Secondary outcomes were safety, reactogenicity and neutralizing antibodies. Findings: Seroconversion rate in vaccinees was 76.3 %after two doses, and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and VOCs alpha, beta, and delta. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. Conclusions: Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000347 Funding: Supported by Finlay Vaccine Institute, BioCubaFarma and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).Declaration of Interests: Authors M.E.T.R., M.G.C., L.V.S., S.P.R, C.V.S, M.T.P.G., J.E.P, E.N.R., A.P.D., G.B.R., I.M.H., Y.M, Y.G.M., B.L.S.V., G.W.C., D.D., A.B., and D.G.R., declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Authors M.R.G., B.P.M., B.S.R., R.G.M., T.H.G., I.O.V., M.D.H., S.F.C., Y.C.R, L.R.N., D.S.M., Y.G.V., T.B.A., Y.V.B., D.G-R., and V.V.B., work at Finlay Vaccine Institute or the Centre of Molecular Immunology, institutions that develop and manufacture the vaccine candidates but they haven’t received an honorarium for this paper. B.S.R., S.F.C., Y.C.R, L.R.N., D.S.M., Y.V.B., D.G.R., D.G-R. and V.V.B., have filed patent applications related to the vaccine SOBERANA 02.Ethics Approval Statement: The phase II clinical trial protocol was reviewed and approved by an ad hoc centralized Research Ethics Committee from the Medical Sciences University, Faculty of Medicine “Manuel Fajardo”, Havana, designed by the Health Innovation Committee from the Cuban Ministry of Health (MINSAP). The Cuban National Regulatory Agency (CECMED) approved the trial and the procedures (reference number: 05.019.20BA, 17th December 2020). The National Clinical Trials Coordinating Center (CENCEC) was responsible for monitoring data accuracy, adherence to the protocol and to Good Clinical Practice. An Independent Data Monitoring Committee (conformed by six external and independent members specialized on clinical practice, epidemiology and statistic) supervised the study. The trial was conducted following the Declaration of Helsinki, Good Clinical Practice and the rules of the Cuban National Immunization Program. During participants recruitment, the potential participants received all relevant information (both orally and written) about the vaccine candidates, and the potential risks and benefits of the trial. All doubts were clarified before enrollment. The decision to participate in the study was voluntary and not remunerated. Written informed consent was obtained from all participants.Trial Registration: https://rpcec.sld.cu/en/trials/RPCEC00000347-En