VacciMonitor: 30 años divulgando ciencia / VacciMonitor: 30 years spreading science

VacciMonitor, producto líder del sello editorial Finlay Ediciones, es una revista arbitrada dedicada a la vacunología y otras disciplinas relacionadas que se reafirma como la única con estas características en Latinoamérica. Existen otras con iguales objetivos editadas por países desarrollados, como Vaccine de la editorial Elsevier (Holanda) y Vacunas, de Doyma (España).1,2 Se fundó en 1992 con el objetivo de divulgar los logros alcanzados por Cuba en el campo de las vacunas; desde esa fecha ha contribuido a visibilizar el impacto de la vacunación en nuestro país y el desarrollo de la industria farmacéutica y biotecnológica que produce gran parte de las vacunas utilizadas en el programa nacional de inmunización.2 En sus inicios tuvo un carácter institucional. En el año 2000 trascendió nuestras fronteras y a partir de ese momento aumentaron los artículos procedentes de otros países1,2. Su frecuencia ha variado, atendiendo principalmente a la disponibilidad de artículos científicos. En los últimos años se ha estabilizado como publicación cuatrimestral.1,2,3 Del año 2005 al 2021 se han publicado 263 artículos científicos, de 31 países y 156 instituciones. El 27,8 por ciento de esta producción es externa a nuestro país y el 72,2 por ciento, interna; de esta última, el 49,4 por ciento corresponde a producción no institucional. En VacciMonitor han publicado autores cubanos y de otros países como México, Venezuela, Malasia, Reino Unido, entre otros. Las Instituciones cubanas que más contribuyen a la revista son: Instituto Finlay de Vacunas, Centro de Ingeniería Genética y Biotecnología, Instituto de Medicina Tropical ¨Pedro Kourí¨, Instituto Superior Politécnico José Antonio Echeverría y Universidad de Ciencias Médicas de La Habana.4) VacciMonitor es una revista a favor de la Ciencia Abierta.5 Acepta manuscritos publicados en archivos de preprints; proporciona un acceso abierto inmediato a su contenido, basado en el principio de que ofrecer al público un acceso libre a las investigaciones ayuda a un mayor intercambio global de conocimiento; el acceso a todos los contenidos de la revista, registro y envío de artículos es totalmente gratuito. Todo el procesamiento de los artículos, su revisión, edición y publicación es libre...(AU)

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.

A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and Neisseria meningitidis outer membrane vesicles.

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

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.

Cross-protection induced by VA-MENGOC-BC® vaccine.

I would like to comment on the article "Commentary: Impact of meningococcal group B OMV vaccines, beyond their brief", DOI: 10.1080/21645515.2017.1381810. The author states that meningococcal group B OMVs vaccines -such as VA-MENGOC-BC®- may induce moderate protection against Neisseria gonorrhoeae. I agree. However, the author states that "there was no evidence of effectiveness in the younger children." The effectiveness of VA-MENGOC-BC® in heterologous contexts has been higher than 80% in individuals older than 4 years old, but the effectiveness in younger children should not be undervalued; it has usually been higher than 60%, and results markedly higher when evaluated based on mortality rates. There is strong evidence that VA-MENGOC-BC® may induce cross-protection against heterologous N. meningitidis strains and N. gonorrhoeae.

Effectiveness of a Serogroup B and C Meningococcal Vaccine Developed in Cuba.

INTRODUCTION Serogroup B meningococcal outer membrane vesicle vaccines have been effective against vaccine-type strains, but their effectiveness against heterologous strains has been controversial. The Cuban VA-MENGOC-BC vaccine is of this type, but also includes meningococcus C capsular polysaccharide. OBJECTIVES Assess the effectiveness of VA-MENGOC-BC in reducing meningococcal disease caused by homologous or heterologous serogroup B strains and its serological effectiveness against meningococcus C. METHODS A review of studies of VA-MENGOC-BC's application in Cuba, Brazil, Uruguay and Colombia was carried out to examine the vaccine's effectiveness in reducing meningococcal disease during serogroup B outbreaks. Serological effectiveness against serogroup C determined in these studies (indicated by bactericidal antibody titers before and after vaccination) was also analyzed. RESULTS VA-MENGOC-BC's effectiveness against homologous serogroup B strains has consistently been greater than 80% in all age groups. Effectiveness in heterologous contexts was also above 80% in individuals aged >4 years. Lower effectiveness in heterologous contexts was found in Brazilian children aged <2 years, although still >50%. Effectiveness increased when assessed based on mortality rates, as well as in cases of clinically severe meningococcal disease. The carrier-state pattern was modified after vaccination with reduction of hypervirulent lineages. Some 60% of infants (aged <1 year) attained protective bactericidal antibody titers against serogroup C. Higher protection rates were achieved in older children. CONCLUSIONS In addition to prevention of meningococcal disease caused by homologous serogroup B strains, VA-MENGOC-BC should be considered for heterologous contexts. It is protective against serogroup C in all age groups. KEYWORDS Neisseria meningitidis, meningococcal disease, meningococcal vaccines, serogroup B meningococcus, serogroup C meningococcus, immunogenicity, bacterial outer membrane proteins, heterologous effects of vaccines, acellular vaccines, Cuba.

Análisis de las causas del insuficiente número de publicaciones nacionales en la revista VacciMonitor / Analysis of causes of the insufficient number of national publications in VacciMonitor journal

VacciMonitor es una revista científica especializada en vacunas, perteneciente a Finlay Ediciones, única con esas características en Latinoamérica. Sin embargo, son pocos los artículos publicados por investigadores cubanos, lo que limita la difusión de los logros que en ese sector de la ciencia ha alcanzado Cuba. Se propuso, por tanto, identificar los motivos por los cuales los investigadores nacionales no publican en ella, mediante encuestas escritas en 40 investigadores de centros científicos y de salud seleccionados en cuatro provincias. VacciMonitor, producto líder de Finlay Ediciones, tiene amplias potencialidades, y si bien está indexada en numerosas bases de datos internacionales, debe alcanzar las más importantes en este campo para hacerla más atractiva entre los investigadores. Las virtudes de la revista son poco conocidas en el ámbito académico nacional, principal causa por la cual los investigadores nacionales no publican, y tampoco están motivados para esto(AU)

VacciMonitor is a scientific journal specialized in vaccines, belonging to Finlay Ediciones, unique with those characteristics in Latin America. However, there are few articles published by Cuban researchers, which restrict the achievements spreading that in that sector of the science our country has obtained. Therefore, we propose to identify the reasons by which the national researchers do not publish in it, by means of written questionnaires applied to 40 researchers of scientific and health centers selected in four provinces. VacciMonitor, the leading product of Finlay Ediciones, has wide potentialities, and it is indexed in numerous international databases, it must reach the most important ones in this field to make it more attractive between the researchers. The journal's virtues are little known in the national academic field, main reason for which the national researchers do not publish, neither they are motivated for it(AU)

Seguridad e inmunogenicidad de una vacuna de polisacárido Vi de salmonella typhi en jóvenes cubanos / Security and immunogenecity of a vaccine of polyssacharide Vi from salmonella typhi in cuban youths

Se realizó un estudio aleatorizado, controlado y a doble ciegas, en adultos jóvenes de 18 a 20 años, con el objetivo de evaluar la reactogenicidad y la inmunogenicidad de vax-TyViâ, vacuna de polisacárido Vi de Salmonella typhi. Se distribuyeron en 3 grupos; inmunizados con una dosis de vax-TyViâ (Instituto Finlay), TYPHIM ViTM (Pasteur-Mérieux) o vax-TETâ (toxoide tetánico). Se tomaron muestras de suero antes y 21 d después de la inmunización. La inmunogenicidad se evaluó en 323 voluntarios mediante un ELISA indirecto. La seroconversión de los que recibieron vax-TyViâ fue 81,97 por ciento y de 65,05 por ciento para TYPHIM ViTM. Los títulos medios geométricos posvacunales fueron 7,41 U/mL (5,92û9,27 U/mL) y 5,41 U/mL (4,35û6,72 U/mL) respectivamente. La seroconversión con vax-TETâ fue 0 por ciento. La reactogenicidad de ambas vacunas polisacarídicas fue baja. Se concluyó que la inmunogenicidad de vax-TyViâ no fue inferior a la de TYPHIM ViTM y su reactogenicidad resultó similar

Valor diagnóstico de las inmunoglobulinas séricas en recién nacidos con sospecha de sepsis prenatal / Diagnostic value of serum immunoglobulins in newborns suspicious of perinatal sepsis

Se escogen 110 neonatos de la Maternidad Provincial desde noviembre de 1987 hasta febrero de 1988, de ellos 32 recién nacidos normales, 38 con sospecha de sepsis prenatal; 30 pretérmino sin antecedentes de ésta y 10 con ella. Se les cuantificó inmunoglobulinas en sangre del cordón umbilical al momento del nacimiento, para evaluar el estado inmunológico y como método diagnóstico de infección adquirida intraútero

Sistema Age HB/Anti-e HB en niños con hepatitis crónica activa / Hbe Ag/anti-Hbe system in children with chronic active hepatitis

En el presente trabajo se determinó el antígeno e del virus productor de la hepatitis B (AgeHB) y su anticuerpo (anti-eHB) en 31 niños menores de 15 años y de ambos sexos, con hepatitis crónica activa (HCA) atendidos en nuestro centro. Se encontró un alto porcentaje de AgeHB positivo (67,7 %) en la totalidad de los pacientes, mientras que los pacientes anti-eHB positivos representaron un porcentaje mucho menor (25,8 %). Los títulos de AgsHB se comportaron con promedios de 1:16 en la mayoría de los pacientes. El estudio realizado muestra una tendencia a la seroconversión del AgeHB en los pacientes con mayor tiempo de evolución

Estudio del sistema HBe Ag/anti-HBe en un grupo de donantes HBs Ag positivo / Study of HBe Ag/anti-HBe in a group of positive HBs Ag donors

Se realizaron las determinaciones del antígeno "e" del virus productor de la hepatitis B (HBeAg) y su anticuerpo (anti-HBe) en 45 donantes de sangre del sexo masculino, aparentemente sanos, en los cuales se detectó con anterioridad el antígeno positivo de superficie (HBsAg). Dichos donantes fueron evaluados serológicamente y mediante biosia hepática. Se pudo demostrar la presencia del HBeAg en el 40 % de los donantes y el anti-HBe en el 44,4 %. En el 13,3 % de los pacientes no pudo demostrarse ninguno de los dos indicadores y en un caso (2,3 %), ambos estaban presentes. Al tener en cuenta la edad, el HBeAg prevaleció en los mayores de 30 años (44,4 %), mientras el anti-HBe fue más frecuente en los menores de edad (55,5 %). El título de HBsAg fue 4 veces mayor como promedio, en los donantes HBe/Ag positivo. Se detectó una amplia relación entre los portadores HBeAg positivo y aquéllos a los que se les diagnosticó una hepatitis crónica activa (HCA) o hepatitis crónica persistente (HCP), en el resultado de la biopsia hepática