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Recorrido de desarrollo para los potentes anticuerpos neutralizantes del VIH dirigidos al V1V2

Nicole A Doria-Rose¹, Chaim A Schramm², Jason Gorman¹

¹1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2].

|March 5, 2014

Resumen

Los investigadores identificaron cómo se desarrollan los anticuerpos neutralizantes dirigidos a las regiones V1V2 de la envolvente del VIH-1. Esto implica seleccionar células B con una larga región H3 que determina la complementariedad, ofreciendo ideas para el diseño de la vacuna contra el VIH-1.

Área de la Ciencia:

Inmunología Inmunología.
Virología Virología.
Desarrollo de Vacunas Desarrollo de Vacunas.

Sus antecedentes:

Los anticuerpos neutralizantes dirigidos a las regiones variables 1 y 2 de la envoltura del VIH-1 (V1V2) son cruciales para el control viral.
El mecanismo preciso por el cual se desarrollan estos potentes anticuerpos ha permanecido en gran medida indefinido.

Objetivo del estudio:

Para dilucidar la vía de desarrollo de los anticuerpos neutralizantes dirigidos por el VIH-1 V1V2.
Comprender las características moleculares requeridas para la neutralización mediada por anticuerpos del VIH-1.

Principales métodos:

Aislamiento y caracterización de doce anticuerpos neutralizantes somáticamente relacionados (CAP256-VRC26.01-12) de un donante infectado por el VIH-1 (CAP256).
Análisis del bucle de unión al antígeno del anticuerpo (región determinante de complementariedad (CDR) H3) y su línea de tiempo de desarrollo.
Correlación de la maduración de anticuerpos con la diversidad de la población viral y la potencia de neutralización.

Principales resultados:

Se identificó un característico bucle protuberante de unión al antígeno aniónico sulfatado de tirosina (CDR H3) en todos los anticuerpos neutralizantes aislados.
El anticuerpo ancestral no mutado, con un CDR H3 de 35 residuos, surgió entre 30 y 38 semanas después de la infección y neutralizó un virus superinfectante.
Se observó una mayor amplitud y potencia de neutralización a la semana 59, después de una maduración de afinidad modesta y una diversificación viral significativa.

Conclusiones:

Los anticuerpos neutralizantes dirigidos por el VIH-1 V1V2 pueden desarrollarse relativamente rápidamente.
La selección inicial de células B que poseen una larga CDR H3 es un paso clave en el desarrollo de anticuerpos.
La hipermutación somática posterior limitada contribuye a la maduración de estos anticuerpos neutralizantes, proporcionando información crítica para las estrategias de vacunación contra el VIH-1.

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