Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

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: a double-blind, randomised, placebo-controlled phase 3 clinical trial.

Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). 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 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. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) 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 circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.

Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children.

OBJECTIVES: 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. METHODS: 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. 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. CONCLUSION: The heterologous scheme was safe and immunogenic in children 3-18 y/o. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000374.

Toxicidad a dosis repetida e inmunogenicidad en Cercopithecus aethiops, del candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo / Repeated dose toxicity and immunogenicity in Cercopithecus aethiops of SARS-CoV-2 SOBERANA 01 (FINLAY-FR-01) vaccine candidate

En el Instituto Finlay de Vacunas se desarrolló el candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo. Este trabajo tuvo como objetivo evaluar la inmunogenicidad y posibles efectos toxicológicos del candidato vacunal SOBERANA 01 (FINLAY-FR-01 en Cercopithecus aethiops. Se utilizaron cinco primates no humanos (hembras), de 1-3 años de edad y 1-4 kg de peso corporal, distribuidos en dos grupos experimentales: Control (Solución Salina Fisiológica) y Tratado SOBERANA 01 (FINLAY-FR-01). El estudio se extendió por 84 días, en un esquema a dosis repetida de cuatro inmunizaciones los días 0, 28, 56 y 70. Se realizaron observaciones clínicas diarias, peso corporal, signos vitales (temperatura rectal, frecuencia respiratoria, y frecuencia cardíaca), exámenes electrocardiográficos, toma de la temperatura del sitio de inyección, musculometría e irritabilidad dérmica. Fueron realizados exámenes de hematología, bioquímica sanguínea, así como estudios inmunológicos. El ensayo concluyó con una supervivencia del 100por ciento, no se manifestaron signos de toxicidad, no hubo variaciones hematológicas, ni de la bioquímica sanguínea asociadas a la sustancia de ensayo. Además, no se observaron efectos locales en el sitio de administración. Por último, el candidato vacunal resultó inmunogénico, ya que se indujeron títulos altos de IgG anti-RBD, así como de la inhibición de la unión de RBD a ACE2(AU)

At Finlay Vaccine Institute has been developed the vaccine candidate SOBERANA 01 (FINLAY-FR-01) against SARS-CoV-2 virus, causing COVID-19. This work aims to evaluate the immunogenicity and possible toxicological effects of the SOBERANA 01 (FINLAY-FR-01) vaccine candidate in Cercopithecus aethiops. Five non-human primates (females) from 1-3 years old and 1-4 kg of body weight were distributed in two experimental groups: Control (Physiological Saline Solution) and Treated (SOBERANA 01 FINLAY-FR-01). The study extended through 84 days, in a repeated dose schedule of four immunizations on days 0, 28, 56, and 70. Daily clinical observations, body weight, vital signs (rectal temperature, respiratory rate, and heart rate), electrocardiographic examinations, temperature of the injection site, musculometry and dermic irritability, were performed. Hematological and blood biochemistry tests, as well as immunological studies were assessed. At the end of the assay 100percent survival was obtained, there were no signs of toxicity neither hematological or blood biochemistry variations associated with the test substance. In addition, no local effects were observed at the administration site. Finally, the vaccine candidate was immunogenic, since high titers of anti-RBD IgG, as well as inhibition of the RBD to ACE2 binding were induced(AU)

Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults.

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).

Safety and immunogenicity of the FINLAY-FR-1A vaccine in COVID-19 convalescent participants: an open-label phase 2a and double-blind, randomised, placebo-controlled, phase 2b, seamless, clinical trial.

BACKGROUND: A phase 1, clinical trial to evaluate FINLAY-FR-1A vaccine in COVID-19 convalescent individuals was completed. Here, we report results of the phase 2, clinical trial. METHODS: We studied 450 convalescent participants with a history of asymptomatic, mild, or moderate COVID-19 at the National Institute of Hematology and Immunology and the National Centre for Sexual Education in Havana, Cuba. The study included adults aged 19-78 years who had recovered from COVID-19 and had had a negative PCR test at least 2 months before the initiation of the study. Phase 2 was done sequentially in two stages. The first stage to assess safety comprised an open, non-controlled phase 2a study in participants aged 60-78 years who received a single dose of the FINLAY-FR-1A vaccine (50 µg of recombinant dimeric receptor binding domain [RBD]). The second stage comprised the placebo-controlled, double-blind, phase 2b trial in participants aged 19-78 years, where participants were randomly assigned (4:1) into two groups: an experimental group vaccinated with a single dose of the FINLAY-FR-1A vaccine, and a control (placebo) group injected with vaccine excipient. The primary outcomes were safety, evaluated 28 days after vaccination by the occurrence of serious adverse events in all participants, and successful immune response, assessed by neutralising antibody ELISA, and defined as half-maximal surrogate virus neutralisation titres of 250 or more. Secondary endpoints included vaccine immunogenicity assessed by ELISA anti-RBD and live-virus neutralisation test. All randomly assigned participants were included in the safety analysis (safety population), and immunogenicity was evaluated in participants without study interruptions (per-protocol population). The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000366-En and WHO-ICTRP and is complete. FINDINGS: From April 9, 2021, to April 17, 2021, 663 COVID-19 convalescent participants were enrolled in the study; 213 participants did not meet the selection criteria and 450 volunteers were recruited. 20 participants aged 60-78 years were included in the open, single-group, phase 2a study and 430 participants were randomly assigned to the experimental (n=344) or control groups (n=86) in the phase 2b study of participants aged 19-78 years. 19 (95%) of 20 phase 2a volunteers achieved a successful immune response after vaccination. No vaccine-associated serious adverse events were reported in the whole study population. Minor adverse events were found, the most common being pain at the injection site (105 [29%] of 364 in the intervention group; 13 [15%] of 86 in the placebo group). A successful immune response was found in 289 (81%) of 358 participants 28 days after vaccination. The vaccine elicited a greater than 31-times increase in anti-RBD-IgG antibodies compared with prevaccination rates, and the seroconversion rate was 302 (84%) of 358 on day 28 after vaccination; the geometric mean titres of live-virus neutralisation test increased from 15·4 (95% CI 10·3-23·2) to 400·3 (272·4-588·1) and high response was found against alpha, beta, and delta variants of concern. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 strengthened the pre-existing natural immunity, with excellent safety profile. FUNDING: Cuba's Ministry of Science, Technology, and Environment.

Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats.

This study evaluates safety of FINLAY-FR-02, a vaccine candidate against SARS-CoV-2 based on the recombinant receptor binding domain conjugated to tetanus toxoid, in a preclinical, repeat-dose toxicity and local tolerance study. Sprague Dawley rats were randomly allocated to three experimental groups: control (receiving physiological saline solution); placebo (receiving all vaccine components except antigens) and vaccine group (receiving three doses of the vaccine candidate, 37.5 µg of RBD) administered intramuscularly in hind limbs at 24 h intervals during three days. We evaluated physiological condition, pain, food and water consumption, body temperature, dermal irritability, injection site temperature and inflammation, immunological response, blood chemistry, relative organ weight, histopathology and immunotoxicology. The product was well tolerated; no clinically relevant changes, pain, local effects or adverse systemic toxicological changes or deaths were observed. These preliminary results permitted the Cuban regulatory authorities to authorize clinical trials in humans.

A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: Safety, reactogenicity and immunogenicity.

BACKGROUND: The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase I clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD). METHODS: We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 µg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 (50 µg d-RBD, three doses); 3) FINLAY-FR-1A-25 (25 µg d-RDB, three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction. RESULTS: Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more subjects with adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules. CONCLUSIONS: Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant. TRIAL REGISTRY: https://rpcec.sld.cu/en/trials/RPCEC00000338-En.

A single dose of SARS-CoV-2 FINLAY-FR-1A vaccine enhances neutralization response in COVID-19 convalescents, with a very good safety profile: An open-label phase 1 clinical trial.

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-γ 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 Innovación (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 reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

Caracterización de cepas de Neisseria meningitidis aisladas de portadores en Cuba durante 20 años / Characterization of Neisseria meningitidis strains isolated from carriers in Cuba during 20 years

Se investigaron los marcadores epidemiológicos de cepas de Neisseria meningitidis aisladas de portadores en Cuba durante 20 años (1982-2002). Se identificaron los serogrupos, serotipos, subtipos e inmunotipos de 331 cepas correspondientes a 2 etapas diferentes: epidémica (1982-1992) y posepidémica (1993-2002). En la epidémica predominó el serogrupo B (67,62 por ciento) y las cepas no agrupables (32,28 por ciento). En la posepidémica prevalecieron las cepas no agrupables (79,65 por ciento) y el serogrupo B (17,26 por ciento) (p< 0,05). El presente estudio es el primero y único hasta el momento, en investigar cepas de Neisseria meningitidis aisladas de portadores antes y después de una campaña nacional masiva de inmunización con VA-MENGOC-BCÒ (vacuna antimeningocócica cubana contra los serogrupos B y C). Los resultados obtenidos aportan datos valiosos al estudio, prevención y control exitoso de la enfermedad meningocócica en Cuba, así como al desarrollo y la evaluación de esta vacuna(AU)

Caracterización de cepas de Neisseria meningitidis aisladas de portadores en Cuba durante 20 años / Characterization of Neisseria meningitidis strains isolated from carriers in Cuba during 20 years

Se investigaron los marcadores epidemiológicos de cepas de Neisseria meningitidis aisladas de portadores en Cuba durante 20 años (1982-2002). Se identificaron los serogrupos, serotipos, subtipos e inmunotipos de 331 cepas correspondientes a 2 etapas diferentes: epidémica (1982-1992) y posepidémica (1993-2002). En la epidémica predominó el serogrupo B (67,62 por ciento) y las cepas no agrupables (32,28 por ciento). En la posepidémica prevalecieron las cepas no agrupables (79,65 por ciento) y el serogrupo B (17,26 por ciento) (p< 0,05). El presente estudio es el primero y único hasta el momento, en investigar cepas de Neisseria meningitidis aisladas de portadores antes y después de una campaña nacional masiva de inmunización con VA-MENGOC-BCÒ (vacuna antimeningocócica cubana contra los serogrupos B y C). Los resultados obtenidos aportan datos valiosos al estudio, prevención y control exitoso de la enfermedad meningocócica en Cuba, así como al desarrollo y la evaluación de esta vacuna

The epidemiological markers of Neisseria meningitidis strains isolated from carriers in Cuba for 20 years (1982-2002) were investigated. There were identified the serogroups, serotypes, subtypes and immunotypes of 331 strains corresponding to 2 different stages: epidemic (1982-1992) and postepidemic (1993-2002). A predominance of serogroup B (67.62 %) and of non-groupable strains (32.28 %) was observed in the epidemic stage, whereas the non-groupable strains (79.65 %) and the serogroup B (17.26 %) (p<0,05) prevailed in the postepidemic stage. This study is the first and the only one up to now that investigates Neisseria meningitidis strains isolated from carriers before and after a national mass campaign of immunization with VA-MENGOC-BCÒ (Cuban antimenigococcal vaccine against the serogroups B and C). The results obtained offered valuable data to the study, prevention and successful control of the meningococcal disease in Cuba, as well as to the development and evaluation of this vaccine

[Characterization of Neisseria meningitidis strains isolated from carriers in Cuba during 20 years]. / Caracterización de cepas de Neisseria meningitidis aisladas de portadores en Cuba durante 20 años.

The epidemiological markers of Neisseria meningitidis strains isolated from carriers in Cuba for 20 years (1982-2002) were investigated. There were identified the serogroups, serotypes, subtypes and immunotypes of 331 strains corresponding to 2 different stages: epidemic (1982-1992) and postepidemic (1993-2002). A predominance of serogroup B (67.62%) and of non-groupable strains (32.28%) was observed in the epidemic stage, whereas the non-groupable strains (79.65%) and the serogroup B (17.26%) (p < 0.05) prevailed in the postepidemic stage. This study is the first and the only one up to now that investigates Neisseria meningitidis strains isolated from carriers before and after a national mass campaign of immunization with VA-MENGOC-BC (Cuban antimenigococcal vaccine against the serogroups B and C). The results obtained offered valuable data to the study, prevention and successful control of the meningococcal disease in Cuba, as well as to the development and evaluation of this vaccine.