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 trialpreprint
Аннотация: SUMMARY 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 8 th to September 30 th , 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. Funding 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.
Год издания: 2021
Авторы: María Eugenia Toledo-Romaní, Mayra García-Carmenate, Carmen Valenzuela‐Silva, Waldemar Baldoquín Rodríguez, Marisel Martínez-Pérez, Meiby Rodríguez-González, Beatriz Paredes-Moreno, Ivis Mendoza-Hernández, Raúl González-Mujica, Oscar Samón-Tabío, Pablo Velazco-Villares, Juan Pablo Bacallao-Castillo, Ernesto Licea-Martín, Misladys Rodríguez-Ortega, Nuris Herrera-Marrero, Esperanza Caballero-González, Liudmila Egües-Torres, Reinaldo Duartes-González, Serguey García-Blanco, Suzette Pérez-Cabrera, Santos Huete-Ferreira, Kirenia Idalmis-Cisnero, Omayda Fonte-Galindo, Dania Meliá-Pérez, Ivonne Rojas-Remedios, Delaram Doroud, Mohammad Mehdí Gouya, Alireza Biglari, Patrick Van der Stuyft, Sonsire Fernández-Castillo, Yanet Climent-Ruíz, Yury Valdés-Balbín, Dagmar García-Rivera, Vicente Vérez-Bencomo
Издательство: Cold Spring Harbor Laboratory
Источник: medRxiv (Cold Spring Harbor Laboratory)
Ключевые слова: SARS-CoV-2 and COVID-19 Research, vaccines and immunoinformatics approaches, COVID-19 Clinical Research Studies
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