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VACCINE-INDUCED CD8+ T CELLS CONTROL AIDS VIRUS REPLICATION
Santana, Marlon G. Veloso de et al. | Date Issued: 2012
Author
Santana, Marlon G. Veloso de
Bonaldo, Myrna C.
Galler, Ricardo
Múltipla autoria - ver em Notas
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto de de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ. Brasil.
Múltipla autoria - ver em Notas
Abstract
Developing a vaccine for HIV may be aided by a complete understanding of those rare cases where some HIV-infected individuals control replication of the virus1–3. The majority of these elite controllers (ECs) express HLA-B*57 or HLA-B*273. These alleles remain by far the most robust associations with low concentrations of plasma virus4,5, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinated 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 controlled replication of the highly pathogenic SIVmac239 clonal 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 Nef RL10-specific response correlated significantly with reduced acute phase viremia. 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 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.
Keywords in Portuguese
AIDS
vacina
CD8+ Células T
Controle
replicação do vírus
 
Keywords
AIDS
vaccine
CD8+ T cells
control replication
virus
 
Publisher
Nature Research
Citation
MUDD, Philip A. et al. Vaccine-induced CD8+ T cells control AIDS virus replication. Nature, v.491, n.7422, 14p, Nov. 2012.
DOI
10.1038/nature11443
ISSN
0028-0836
Notes
AUTHORS - Philip A. Mudd1,2, Mauricio A. Martins3, Adam J. Ericsen1, Damien C. Tully4, Karen A. Power4, Alex T. Bean1, Shari M. Piaskowski1, Lijie Duan5, Aaron Seese4, Adrianne D. Gladden4, Kim L. Weisgrau1, Jessica R. Furlott1, Young-il Kim6, Marlon G. Veloso de Santana7, Eva Rakasz8, Saverio Capuano III8, Nancy A. Wilson1,8, Myrna C. Bonaldo7, Ricardo Galler9, David B. Allison10, Michael Piatak Jr.11, Ashley T. Haase5, Jeffrey D. Lifson11, Todd M. Allen4, and David I. Watkins3 - AFFILIATIONS - 1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711 2Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI 53705 3Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136 4Ragon Institute of MGH, MIT and Harvard, Boston, MA 02129 5Department of Microbiology, University of Minnesota, Minneapolis, MN 55455 6Department of Medicine, Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 7Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz—FIOCRUZ, Rio de Janeiro, Brazil 8Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711 9Instituto de Tecnologia em Imunobiológicos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil 10Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294 11AIDS and Cancer Virus Program, SAIC Frederick, Inc., National Cancer Institute, Frederick, MD 21702.