From Nature: Vaccine-induced CD8+ T cells control AIDS virus replication

http://www.ncbi.nlm.nih.gov/pubmed/23023123

Nature. 2012 Nov 1;491(7422):129-33. doi: 10.1038/nature11443. Epub 2012 Sep 30.

Vaccine-induced CD8+ T cells control AIDS virus replication.

Mudd PA, Martins MA, Ericsen AJ, Tully DC, Power KA, Bean AT, Piaskowski SM, Duan L, Seese A, Gladden AD, Weisgrau KL, Furlott JR, Kim YI, Veloso de Santana MG, Rakasz E, Capuano S 3rd, Wilson NA, Bonaldo MC, Galler R, Allison DB, Piatak M Jr, Haase AT, Lifson JD, Allen TM, Watkins DI.

Source

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.

Abstract

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.