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We evaluated response to a single dose of the FINLAY-FR-1A recombinant dimeric-RBD base vaccine during a phase I clinical trial with 30 COVID-19 convalescents, to test its capacity for boosting natural immunity. This short report shows: a) an excellent safety profile one month after vaccination for all participants, similar to that previously found during vaccination of naïve individuals; b) a single dose of vaccine induces a >20 fold increase in antibody response one week after vaccination and remarkably 4-fold higher virus neutralization compared to the median obtained for Cuban convalescent serum panel. These preliminary results prompt initiation of a phase II trial in order to establish a general vaccination protocol for convalescents.

Background: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. Methods: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Findings: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-I³ and TNF-α. Interpretation: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. Funding: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. Antecedentes: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfeccion, evaluamos la vacuna FINLAY-FR-1A en un ensayo clinico. Metodos: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 anos: convalecientes de COVID-19 leve y convalecientes asintomaticos, ambos con prueba PCR positiva al momento del diagnostico; e individuos con infeccion subclinica detectada por IgG especifica viral. Los participantes recibieron una dosis unica por via intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de union al receptor recombinante dimerico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 dias despues de la vacunacion. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y despues de la vacunacion, se evaluo por ELISA y mediante la prueba de neutralizacion del virus vivo. Tambien se evaluo la respuesta de celulas T efectoras. Registro Publico Cubano de Ensayos Clinicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Resultados: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los mas comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimulo un incremento >21 veces de los anticuerpos IgG anti-RBD 28 dias despues de la vacunacion. La mediana de los titulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron titulos de neutralizacion viral superiores a 1:160 en 24 (80%) de los participantes. Tambien hubo un aumento en las celulas T especificas de RBD que producen IFN-I³ y TNF-α. Interpretacion: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzo eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. Financiamiento: Se recibio un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministerio de Ciencia, Tecnologia y Medio Ambiente, Cuba.