RESUMO
BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- 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 ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (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 variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. 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: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).
Assuntos
COVID-19 , Vacinas , Adulto , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Imunoglobulina GRESUMO
La bioimpedancia eléctrica es una técnica no invasiva que permite analizar la composición corporal de pacientes en hemodiálisis. Se estudiaron 15 pacientes estables en hemodiálisis después de tratamiento hemodialítico durante 1 año (5 mujeres y 10 hombres con más de 6 meses en tratamiento) para determinar el estado hídrico mediante bioimpedancia. Se realizaron 3 mediciones en el año. Se aplicó una corriente de 200 µA para una frecuencia única de 50 kHz. Se calculó el volumen extracelular, el intracelular y el volumen total de agua. Se compararon los resultados con la fórmula de Watson y el "peso seco" obtenido por "estimación clínica" con el peso poshemodiálisis. La morbilidad intradialítica fue considerada durante el tiempo de estudio. Se encontró gran estabilidad de los resultados obtenidos por bioimpedancia eléctrica durante el estudio. El volumen total de agua fue sobreestimado por la fórmula de Watson. El peso poshemodiálisis y el obtenido por "estimación clínica" fueron muy cercanos. Existió disminución gradual de la morbilidad intradialítica durante el año de estudio.
Electric bioimpedance is a non-invasive technique to analyze the body composition of hemodialysis patients. A total of 15 patients after hemodialysis treatment were studied over a year (5 women and 10 men with more than 6 months of treatment) to determine the hydration status by bioimpedance. During this year three measurements were performed. A 200 µA was applied to a single frequency of 50 kHz. The extracellular, the intracellular volume as well as the total volume of water were estimated. Results were compared with the Watson's formula and the "dry weight" post-hemodialysis. Intra-dialysis morbidity was considered during the study time. We found a great stability of results achieved by electric bioimpedance during the study. Water total volume was overrated by Watson's formula. Post-hemodialysis weight and that achieved by "clinical estimation" were very close. There was a gradual decrease of intra-dialysis morbidity during the study year.
RESUMO
La bioimpedancia eléctrica es una técnica no invasiva que permite analizar la composición corporal de pacientes en hemodiálisis. Se estudiaron 15 pacientes estables en hemodiálisis después de tratamiento hemodialítico durante 1 año (5 mujeres y 10 hombres con más de 6 meses en tratamiento) para determinar el estado hídrico mediante bioimpedancia. Se realizaron 3 mediciones en el año. Se aplicó una corriente de 200 µA para una frecuencia única de 50 kHz. Se calculó el volumen extracelular, el intracelular y el volumen total de agua. Se compararon los resultados con la fórmula de Watson y el peso seco obtenido por estimación clínica con el peso poshemodiálisis. La morbilidad intradialítica fue considerada durante el tiempo de estudio. Se encontró gran estabilidad de los resultados obtenidos por bioimpedancia eléctrica durante el estudio. El volumen total de agua fue sobreestimado por la fórmula de Watson. El peso poshemodiálisis y el obtenido por estimación clínica fueron muy cercanos. Existió disminución gradual de la morbilidad intradialítica durante el año de estudio(AU)
Electric bioimpedance is a non-invasive technique to analyze the body composition of hemodialysis patients. A total of 15 patients after hemodialysis treatment were studied over a year (5 women and 10 men with more than 6 months of treatment) to determine the hydration status by bioimpedance. During this year three measurements were performed. A 200 µA was applied to a single frequency of 50 kHz. The extracellular, the intracellular volume as well as the total volume of water were estimated. Results were compared with the Watson's formula and the dry weight post-hemodialysis. Intra-dialysis morbidity was considered during the study time. We found a great stability of results achieved by electric bioimpedance during the study. Water total volume was overrated by Watson's formula. Post-hemodialysis weight and that achieved by clinical estimation were very close. There was a gradual decrease of intra-dialysis morbidity during the study year(AU)
