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Las células T CD8+ inducidas por la vacuna controlan la replicación del virus del SIDA
Philip A Mudd1, Mauricio A Martins, Adam J Ericsen
1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Nature
|October 2, 2012
Resumen
El desarrollo de vacunas para el virus de la inmunodeficiencia humana (VIH) puede avanzar mediante el estudio de los controladores de élite. Este estudio muestra que las respuestas dirigidas de las células T CD8 ((+)) pueden controlar la replicación del virus de inmunodeficiencia simio (SIV) en macacos.
Área de la Ciencia:
- Inmunología Inmunología.
- Virología Virología.
- Vacunología Vacunología.
Sus antecedentes:
- Algunos individuos controlan naturalmente la replicación del virus de la inmunodeficiencia humana (VIH), denominados controladores de élite.
- El control de élite está fuertemente asociado con alelos específicos del antígeno leucocitario humano (HLA), como el HLA-B*27.
- Los mecanismos precisos que subyacen a este control viral no se comprenden completamente.
Objetivo del estudio:
- Investigar si las respuestas de las células T CD8 ((+) estrechamente dirigidas pueden controlar la replicación del virus de la inmunodeficiencia simiana (SIV).
- Para explorar el papel de Mamu-B*08, un modelo animal para HLA-B*27, en el control viral.
Principales métodos:
- Los macacos rhesus indios que expresan Mamu-B*08 fueron vacunados con tres epítopos de células T Mamu-B*08 restringidas CD8 ((+).
- Se monitoreó la replicación viral del patógeno SIVmac239.
- Se cuantificaron las frecuencias de las células T CD8 ((+)) dirigidas a los epítopos Vif y Nef en la sangre, los ganglios linfáticos y el colon.
- Se analizaron la carga viral y las mutaciones de escape de epítopos.
Principales resultados:
- Los macacos vacunados demostraron control sobre la replicación del SIV.
- Frecuencias altas de células T CD8 (((+) dirigidas a los epítopos Vif y Nef correlacionados con el control viral.
- Una respuesta específica del epitopo de Nef (RL10) correlacionada con una reducción de la viremia aguda.
- La pérdida del control viral en dos animales coincidió con las mutaciones de escape viral en los epítopos objetivo.
Conclusiones:
- Las respuestas de las células T inducidas por la vacuna, específicas para el virus CD8 (((+) que se dirigen a los epítopos clave pueden controlar efectivamente la replicación del SIV.
- Este hallazgo respalda el potencial de vacunas dirigidas basadas en células T contra el VIH / SIDA.
- El estudio destaca la importancia de los epítopos específicos de células T en el control de las infecciones lentivirales.
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