Vaccine-induced CD8^sup +^ T cells control AIDS virus replication

• Published in: Nature (London) 2012-11, Vol.491 (7422), p.129
• Main Authors: 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, de Santana, Marlon G Veloso, 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
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino acids; Animal care; Animal models; HIV; Human immunodeficiency virus; Infections; Lymph nodes; Lymphocytes; Mutation; Plasma; T cell receptors; Vaccines
• ISSN: 0028-0836; 1476-4687

Developing a vaccine for humanimmunodeficiency 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 control6, 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 NefRL10 epitope (Nefamino 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. [PUBLICATION ABSTRACT]