•FINLAY-FR-2 conjugate vaccine is safe and immunogenic in children 3-18 years old.•The third dose with FINLAY-FR-1A (dimer receptor binding domain vaccine) increases the immune response.•The ...heterologous three-dose schedule elicited specific T-cell response.•This vaccination elicits neutralizing antibodies vs the Delta and Omicron variants of concern.•Immune response in children is non-inferior to young adults.
To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines.
A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results.
Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval CI 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron.
The heterologous scheme was safe and immunogenic in children 3-18 y/o.
https://rpcec.sld.cu/trials/RPCEC00000374
Multiple vaccine candidates against COVID-19 are currently being evaluated. We evaluate the safety and immunogenicity protein of a novel SARS-CoV-2 virus receptor-binding domain (RBD) vaccine.
A ...phase 1-2, randomised, double-blind, placebo-controlled trial was carried out in “Saturnino Lora” Hospital, Santiago de Cuba, Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1:1, in blocks) to three groups: placebo, 25 µg and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0·5 mL in the deltoid region. During the first phase, two immunization schedules were studied: 0-14-28 days (short) and 0-28-56 days (long). In phase 2, only the short schedule was evaluated. The organoleptic characteristics and presentations of vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained masked during the study period. The main endpoints were safety and the proportion of subjects with seroconversion of anti-RBD IgG antibodies, analysed by intention to treat and per protocol, respectively. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000346.
Between Dec 7, 2020, and Feb 9, 2021, 792 subjects were included; 132 (66 in each vaccination schedule, divided into 22 for each group) in phase 1, and 660 (220 in each group plus 66 from the short scheme of phase 1) in phase 2. The product was well tolerated. No severe adverse events were reported. During phase 1, the incidence of adverse events in the 25 µg, 50 µg, and placebo arms for the short schedule were 6/22 (27·3%), 6/22 (27·3%), 3/22 (13·6%), respectively, and for the long schedule were 8/22 (36·4%), 9/22 (40·9%), 4/22 (18·2%), respectively. In phase 2, adverse reactions were reported by 53/242 (21·9%), 75/242 (31·0%) and 41/242 (16·9%) participants in the 25 µg, 50 µg, and placebo group, respectively. Adverse reactions were minimal, mostly mild, and from the injection site, which resolved in the first 24-48 hours. In phase 1, seroconversion at day 56 was seen in 95·2% of the participants (20/21) in the 50 μg group, 81% (17/21) in the 25 μg group, and none in the placebo group (0/22). For the long schedule, seroconversion at day 70 was seen in 100% of the participants (21/21) in the 50 μg group, 94·7% (18/19) in the 25 μg group, and none in the placebo group (0/22). In phase 2, seroconversion of anti-RBD IgG antibodies at day 56 was seen in 89·2% of the participants in the 50 μg group (214/240; 95% CI 84·5-92·82), 77·7% in the 25 μg group (185/238; 72·0-82·9) and 4·6% in the placebo group (11/239; 2·3-8·1). Compared with the placebo arm, the differences in the proportion of participants with seroconversion were 73·1% (95% CI 66·8-79·5) and 84·6% (79·4-89·7) in the 25 μg and 50 μg groups, respectively. The seroconversion rate in the 50 μg group was significantly higher than in the 25 μg group (p=0·0012).
The Abdala vaccine was safe, well tolerated, and induced humoral immune responses against SARS-CoV-2. These results, in the context of the emergency COVID-19 pandemic, support the 50 μg dose, applied in a 0-14-28 days schedule, for further clinical trials to confirm vaccine efficacy.
Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.
As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial.
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.
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-γ and TNF-α.
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.
Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.
RESUMEN Introducción. La Organización Mundial de la Salud (OMS) recomienda la realización de estudios representativos a nivel nacional para estimar la prevalencia de la resistencia pretratamiento del ...VIH a los antirretrovirales (PDR) para evaluar la efectividad de las terapias de primera línea. El objetivo del presente estudio fue determinar la prevalencia de PDR en adultos cubanos infectados por el VIH-1. Métodos. Se determinó la resistencia del VIH a los antirretrovirales a 610 pacientes cubanos en dos períodos de tiempo (469 pacientes entre 2009-2016 y 141 pacientes durante la encuesta nacional de PDR del VIH-1 efectuada durante el año 2017, según las recomendaciones emitidas por la OMS). Resultados y Discusión. En el período 2009-2016, el 19 % de los pacientes presentaron virus con alguna mutación asociada a la PDR del VIH-1 a los antirretrovirales (10,4 % a algún inhibidor de la transcriptasa inversa análogo de nucleósidos (ITIAN), 12,8 % a algún inhibidor de la transcriptasa inversa no análogo de nucleósidos (ITINAN), 2,8 % a algún inhibidor de proteasa (IP). En el año 2017, la prevalencia de PDR fue de 29,8 % (95 %, IC 22,3-38,1). La prevalencia fue de 10,6 % (95 %, IC 6,07-16,9) para algún ITIAN, 23,4 % (95 %, IC 16,7-31,3) para algún ITINAN y 1,4 % (95 %, IC 0,17-5,03) para algún IP. Se concluyó que los valores por encima del 10 % en la prevalencia de la PDR a los ITINAN evidencia el comprometimiento de la primera línea de terapia antirretroviral empleada en Cuba y la necesidad de buscar nuevas opciones de tratamiento.
Introducción. La Organización Mundial de la Salud (OMS) recomienda la realización de estudios representativos a nivel nacional para estimar la prevalencia de la resistencia pre- tratamiento del VIH a ...los antirretrovirales (PDR) para evaluar la efectividad de las terapias de primera línea. El objetivo del presente estudio fue determinar la prevalencia de PDR en adultos cubanos infectados por el VIH-1. Métodos. Se determinó la resistencia del VIH a los antirretrovirales a 610 pacientes cubanos en dos períodos de tiempo (469 pacientes entre 2009-2016 y 141 pacientes durante la encuesta nacional de PDR del VIH-1 efectuada durante el año 2017, según las recomendaciones emitidas por la OMS). Resultados y Discusión. En el período 2009-2016, el 19 % de los pacientes presentaron virus con alguna mutación aso- ciada a la PDR del VIH-1 a los antirretrovirales (10,4 % a algún inhibidor de la transcriptasa inversa análogo de nucleósidos (ITIAN), 12,8 % a algún inhibidor de la transcriptasa inversa no análogo de nucleósidos (ITINAN), 2,8 % a algún inhibidor de proteasa (IP). En el año 2017, la prevalencia de PDR fue de 29,8 % (95 %, IC 22,3-38,1). La prevalencia fue de 10,6 % (95 %, IC 6,07-16,9) para algún ITIAN, 23,4 % (95 %, IC 16,7-31,3) para algún ITINAN y 1,4 % (95 %, IC 0,17-5,03) para algún IP. Se concluyó que los valores por encima del 10 % en la prevalencia de la PDR a los ITINAN evidencia el comprometimiento de la primera línea de terapia antirretro- viral empleada en Cuba y la necesidad de buscar nuevas opciones de tratamiento.
SOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I ...and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols.
We performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 μg RBD-conjugated to 20 μg of TT) in 40 subjects, 19–59-years-old. Phase IIa was open-label including 100 volunteers 19–80-years, receiving two doses of SOBERANA 02–25 μg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response.
The most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects.
In phase-I SOBERANA 02–25 µg elicited higher immune response than SOBERANA 02–15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02–25 µg even in 60–80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization.
SOBERANA 02 was safe and immunogenic in persons aged 19–80 years, eliciting neutralizing antibodies and specific T-cell response. Highest immune responses were obtained in the heterologous three doses protocol.
Trial registry: https://rpcec.sld.cu/trials/RPCEC00000340, https://rpcec.sld.cu/trials/RPCEC00000347
La validación de la capacidad de aclaramiento viral de los procesos de fabricación de productos biológicos constituye un requisito regulatorio en Cuba. Se recomienda introducir la pasteurización en ...los procesos de producción de la albúmina como un método capaz de inactivar virus; por ello, el objetivo del estudio fue validar la capacidad de inactivación viral de la etapa de pasteurización del proceso de producción de la albúmina humana al 20 y 25 %. Los modelos virales que abarcan los posibles contaminantes de la materia prima, se diluyeron 1:10 en la albúmina en sus 2 concentraciones y se sometieron a tratamiento térmico a 60 °C durante 10 h. Se tomaron muestras a diferentes intervalos de tiempo para la confección de las curvas de cinética de inactivación. Se determinó el factor de reducción aportado por la pasteurización para cada virus. El tratamiento a 60 °C de la albúmina al 20 y 25 % disminuyó significativamente la carga viral inicial con que se retó la etapa, con valores de p< 0,002 y p< 0,021, respectivamente, y se obtuvieron factores de reducción superiores a 4 log del título de todos los virus. La etapa de pasteurización le aportó a la albúmina humana al 20 y 25 % un adecuado nivel de seguridad.
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