Author | Martins, Maurício A. | |
Author | Tully, Damien C. | |
Author | Cruz, Michael A. | |
Author | Power, Karen A. | |
Author | Santana, Marlon G. Veloso de | |
Author | Bean, David J. | |
Author | Ogilvie, Colin B. | |
Author | Gadgil, Rujuta | |
Author | Lima, Noemia S. | |
Author | Magnani, Diogo M. | |
Author | Ejima, Keisuke | |
Author | Allison, David B. | |
Author | Platak Jr., Michael | |
Author | Altman, John D. | |
Author | Parks, Christopher L. | |
Author | Rakasz, Eva G. | |
Author | Capuano III, Saverio | |
Author | Galler, Ricardo | |
Author | Bonaldo, Myrna C. | |
Author | Lifson, Jeffrey D. | |
Author | Allen, Todd M. | |
Author | Watkins, David I. | |
Access date | 2016-06-02T13:02:47Z | pt_BR |
Access date | 2016-06-03T12:34:19Z | |
Available date | 2016-06-02T13:02:47Z | pt_BR |
Available date | 2016-06-03T12:34:19Z | |
Document date | 2015 | pt_BR |
Citation | MARTINS, Maurício A. et al. Vaccine-induced simian immunodeficiency virus-specific CD8 TCell responses focused on a single nef epitope select for escape variants shortly after infection. Journal of Virology, v. 89, n. 21, p. 10802-10820, Nov. 2015. | pt_BR |
ISSN | 0022-538X | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/14437 | |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Vírus da imunodeficiência símia (SIV) | pt_BR |
Subject in Portuguese | Células CD8+ T | pt_BR |
Title | Vaccine-induced simian immunodeficiency virus-specific CD8 TCell responses focused on a single nef epitope select for escape variants shortly after infection | en_US |
Type | Article | pt_BR |
DOI | 10.1128/JVI.01440-15 | pt_BR |
Abstract | Certain major histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B*27) are enriched among human immunodeficiency virus type 1 (HIV-1)-infected individuals who suppress viremia without treatment (termed "elite controllers" [ECs]). Likewise, Mamu-B*08 expression also predisposes rhesus macaques to control simian immunodeficiency virus (SIV) replication. Given the similarities between Mamu-B*08 and HLA-B*27, SIV-infected Mamu-B*08(+) animals provide a model to investigate HLA-B*27-mediated elite control. We have recently shown that vaccination with three immunodominant Mamu-B*08-restricted epitopes (Vif RL8, Vif RL9, and Nef RL10) increased the incidence of elite control in Mamu-B*08(+) macaques after challenge with the pathogenic SIVmac239 clone. Furthermore, a correlate analysis revealed that CD8(+) T cells targeting Nef RL10 was correlated with improved outcome. Interestingly, this epitope is conserved between SIV and HIV-1 and exhibits a delayed and atypical escape pattern. These features led us to postulate that a monotypic vaccine-induced Nef RL10-specific CD8(+) T-cell response would facilitate the development of elite control in Mamu-B*08(+) animals following repeated intrarectal challenges with SIVmac239. To test this, we vaccinated Mamu-B*08(+) animals with nef inserts in which Nef RL10 was either left intact (group 1) or disrupted by mutations (group 2). Although monkeys in both groups mounted Nef-specific cellular responses, only those in group 1 developed Nef RL10-specific CD8(+) T cells. These vaccine-induced effector memory CD8(+) T cells did not prevent infection. Escape variants emerged rapidly in the group 1 vaccinees, and ultimately, the numbers of ECs were similar in groups 1 and 2. High-frequency vaccine-induced CD8(+) T cells focused on a single conserved epitope and therefore did not prevent infection or increase the incidence of elite control in Mamu-B*08(+) macaques.
IMPORTANCE:
Since elite control of chronic-phase viremia is a classic example of an effective immune response against HIV/SIV, elucidating the basis of this phenomenon may provide useful insights into how to elicit such responses by vaccination. We have previously established that vaccine-induced CD8(+) T-cell responses against three immunodominant epitopes can increase the incidence of elite control in SIV-infected Mamu-B*08(+) rhesus macaques—a model of HLA-B*27-mediated elite control. Here, we investigated whether a monotypic vaccine-induced CD8(+) T-cell response targeting the conserved "late-escaping" Nef RL10 epitope can increase the incidence of elite control in Mamu-B*08(+) monkeys. Surprisingly, vaccine-induced Nef RL10-specific CD8(+) T cells selected for variants within days after infection and, ultimately, did not facilitate the development of elite control. Elite control is, therefore, likely to involve CD8(+) T-cell responses against more than one epitope. Together, these results underscore the complexity and multidimensional nature of virologic control of lentivirus infection. | pt_BR |
Affilliation | University of Miami. Department of Pathology. Miami, FL, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | University of Miami. Department of Pathology. Miami, FL, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | University of Miami. Department of Pathology. Miami, FL, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | University of Miami. Department of Pathology. Miami, FL, USA. | pt_BR |
Affilliation | University of Alabama. Department of Biostatistics. Section on Statistical Genetics. Birmingham, AL, USA. | pt_BR |
Affilliation | University of Alabama. Department of Biostatistics. Section on Statistical Genetics. Birmingham, AL, USA. | pt_BR |
Affilliation | Frederick National Laboratory. Leidos Biomedical Research, Inc. AIDS and Cancer Virus Program. Frederick, MD, USA. | pt_BR |
Affilliation | Emory University. Department of Microbiology and Immunology. Atlanta, GA, USA. | pt_BR |
Affilliation | Brooklyn Army Terminal. AIDS Vaccine Design and Development Laboratory. International AIDS Vaccine Initiative. Brooklyn, NY, USA. | pt_BR |
Affilliation | University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA. | pt_BR |
Affilliation | University of Wisconsin-Madison. Wisconsin National Primate Research Center. Madison, WI, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Flavivírus. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Frederick National Laboratory. Leidos Biomedical Research, Inc. AIDS and Cancer Virus Program. Frederick, MD, USA. | pt_BR |
Affilliation | Ragon Institute of MGH, MIT and Harvard. Cambridge, MA, USA. | pt_BR |
Affilliation | University of Miami. Department of Pathology. Miami, FL, USA. | pt_BR |
Subject | CD8+ T cells | en_US |
Subject | simian immunodeficiency virus (SIV) | en_US |
Subject | HIV-1 | en_US |
Subject | Monkeys | en_US |
Subject | Vaccine | en_US |
e-ISSN | 1098-5514 | pt_BR |