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Vaccine-induced CD8+ T cells control AIDS virus replication.
Mudd, Philip A; Martins, Mauricio A; Ericsen, Adam J; Tully, Damien C; Power, Karen A; Bean, Alex T; Piaskowski, Shari M; Duan, Lijie; Seese, Aaron; Gladden, Adrianne D; Weisgrau, Kim L; Furlott, Jessica R; Kim, Young-il; Veloso de Santana, Marlon G; Rakasz, Eva; Capuano, Saverio; Wilson, Nancy A; Bonaldo, Myrna C; Galler, Ricardo; Allison, David B; Piatak, Michael; Haase, Ashley T; Lifson, Jeffrey D; Allen, Todd M; Watkins, David I.
Afiliación
  • Mudd PA; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.
Nature ; 491(7422): 129-33, 2012 Nov 01.
Article en En | MEDLINE | ID: mdl-23023123
Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus. Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27 (ref. 3). These alleles remain by far the most robust associations with low concentrations of plasma virus, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control, with three Mamu-B*08-restricted CD8(+) T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8(+) T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8(+) T-cell response against the Nef RL10 epitope (Nef amino acids 137-146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8(+) T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8(+) T-cell responses can control replication of the AIDS virus.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Síndrome de Inmunodeficiencia Adquirida del Simio / Síndrome de Inmunodeficiencia Adquirida / Virus de la Inmunodeficiencia de los Simios / Vacunas contra el SIDA / Vacunas contra el SIDAS / Linfocitos T CD8-positivos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Síndrome de Inmunodeficiencia Adquirida del Simio / Síndrome de Inmunodeficiencia Adquirida / Virus de la Inmunodeficiencia de los Simios / Vacunas contra el SIDA / Vacunas contra el SIDAS / Linfocitos T CD8-positivos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido