Description | 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. | pt_BR |
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. | pt_BR |