Publication Date:
2012-10-02
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883109/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 3rd -- Wilson, Nancy A -- Bonaldo, Myrna C -- Galler, Ricardo -- Allison, David B -- Piatak, Michael Jr -- Haase, Ashley T -- Lifson, Jeffrey D -- Allen, Todd M -- Watkins, David I -- HHSN261200800001E/PHS HHS/ -- P51 OD011106/OD/NIH HHS/ -- R01 AI076114/AI/NIAID NIH HHS/ -- R24 RR015371/RR/NCRR NIH HHS/ -- R37 AI052056/AI/NIAID NIH HHS/ -- RR015371/RR/NCRR NIH HHS/ -- T32 GM008692/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 1;491(7422):129-33. doi: 10.1038/nature11443. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023123" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/*immunology
;
Acquired Immunodeficiency Syndrome/*virology
;
Animals
;
CD8-Positive T-Lymphocytes/*immunology
;
Disease Models, Animal
;
Epitopes, T-Lymphocyte/immunology
;
Female
;
HIV-1/immunology
;
HLA-B27 Antigen/immunology
;
Humans
;
Immunodominant Epitopes/immunology
;
Macaca mulatta/immunology/virology
;
Male
;
SAIDS Vaccines/*immunology
;
Simian Acquired Immunodeficiency Syndrome/immunology/*prevention &
;
control/virology
;
Simian Immunodeficiency Virus/growth & development/*immunology/pathogenicity
;
Viral Load
;
Viremia/immunology/prevention & control
;
Virus Replication/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
