Wednesday, 20 July 2022 15:26

Un equipo del CSIC demuestra en macacos que la combinación de vacunas es clave para lograr una buena respuesta inmune frente al VIH

La investigadora Beatriz Perdiguero en el CNB-CSIC La investigadora Beatriz Perdiguero en el CNB-CSIC CNB-CSIC
  • La combinación de vacunas y el período de administración son determinantes para conseguir respuestas inmunes tempranas y duraderas

Un equipo de investigadores del Centro Nacional de Biotecnología del CSIC, junto con un consorcio internacional, ha demostrado en macacos que la combinación de vacunas y el período de administración son determinantes para lograr respuestas inmunes tempranas y de memoria frente al virus de la inmunodeficiencia humana (VIH), el virus causante del SIDA. Los resultados se publican en la revista Frontiers in Immunology, con la doctora Beatriz Perdiguero como primera autora y con el virólogo Mariano Esteban como autor corresponsable, ambos del CSIC. El proyecto vacunal ha sido financiado por la Fundación Gates.

“El estudio en macacos Rhesus demuestra la importancia de la combinación de vacunas y los tiempos de administración para conseguir mejores respuestas inmunes frente al VIH”, explica Esteban. “Este resultado es aplicable a otras vacunas”, añade.

“Para controlar la infección por el VIH se requiere una respuesta inmune potente mantenida en el tiempo, con generación de anticuerpos neutralizantes de amplio espectro de acción, y activación de linfocitos B y T de memoria específicos frente al virus”, detalla el virólogo.

Debido a la importancia de la infección por VIH y la enfermedad que provoca, el SIDA, es fundamental desarrollar una vacuna eficaz frente a este patógeno, que produce unas 700.000 muertes anuales.

“En este proyecto internacional, europeo y americano, hemos caracterizado en macacos el efecto de combinar tres tipos de vacunas: una basada en ácido nucleico (ADN), otra en un vector de poxvirus no replicativo en células humanas (NYVAC) y una tercera en la proteína Env de la envoltura del VIH junto con adyuvante”, enumera Esteban.

“Las preguntas principales que nos hemos planteado han sido las siguientes: si la co-administración de la proteína Env junto con la vacuna de ADN o de NYVAC puede acelerar la inducción de anticuerpos y si se consigue mejorar la calidad de las respuestas inmunes que se correlacionen con protección añadiendo dosis de recuerdo tardías”, indica el virólogo.

En este estudio, distintas combinaciones de ADN, del vector NYVAC y de la proteína Env fueron administradas por ruta intramuscular a macacos Rhesus repartidos en grupos de 8 a 12 animales, inoculados a las semanas 0, 4, 12 y 24. Además, se estudió el efecto que la re-inmunización a las 36 y 48 semanas podía tener sobre la mejora en la respuesta inmune por dosis de recuerdo tardías.

Como indica la doctora Perdiguero: “Los distintos regímenes indujeron unas respuestas inmunes amplias, polifuncionales y equilibradas en cuanto a la activación de linfocitos T CD4 y CD8, una alta producción en plasma de anticuerpos de unión a los dominios V1/V2 de la proteína Env, y más modesta de anticuerpos dependientes de células citotóxicas (ADCC) y de anticuerpos neutralizantes”. Se considera a estos marcadores inmunes como esenciales para conseguir un control de la infección por VIH.

Los autores concluyen que la utilización de la proteína Env como primera dosis de vacunación administrada conjuntamente con ADN o con el vector NYVAC representa un protocolo optimizado de inmunización frente al VIH.

Como comenta el doctor Esteban: “Estos estudios son importantes en el desarrollo de estrategias de vacunación frente al VIH, al potenciar los distintos componentes del sistema inmune que pueden controlar la resistencia del virus a la acción de las vacunas. Además, estos estudios aportan información sobre cómo la administración continuada de vacunas no incrementa de forma exponencial la respuesta inmune inducida más allá de la cuarta dosis, lo que puede ser aplicable al efecto que el aumento de dosis de recuerdo puede tener frente al SARS-CoV-2”.

CSIC Comunicación

Referencia científica:
Beatriz Perdiguero, Benedikt Asbach, Carmen E. Gomez, Josef Köstler, Susan Barnett, Marguerite Koutsoukos, Deborah E. Weiss, Anthony D. Cristillo, Kathryn E. Foulds, Mario Roederer, David C. Montefiori, Nicole L. Yates, Guido Ferrari, Xiaoying Shen, Sheetal Sawant, Georgia D. Tomaras, Alicia Sato, William J. Fulp, Raphael Gottardo, Song Ding, Jonathan L. Heeney, Giuseppe Pantaleo, Mariano Esteban and Ralf Wagner. Early and long-term HIV-1 immunogenicity induced in macaques by the combined administration of DNA, NYVAC and Env protein-based vaccine candidates: The AUP512 Study. Frontiers in Immunology. DOI: 10.3389/fimmu.2022.93962

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