Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8+ T-Cell Responses Focused on a Single Nef Epitope Select for Escape Variants Shortly after Infection

Mauricio A. Martins, Damien C. Tully, Michael A. Cruz, Karen A. Power, G. Veloso de Santana Marlon, David J. Bean, Colin B. Ogilvie, Rujuta Gadgil, Noemia S. Lima, Diogo M. Magnani, Keisuke Ejima, David B. Allison, Michael Piatak, John D. Altman, Christopher L. Parks, Eva G. Rakasz, Saverio Capuano, Ricardo Galler, Myrna C. Bonaldo, Jeffrey D. LifsonTodd M. Allen, David I. Watkins

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Certainmajor histocompatibility complex class I (MHC-I) alleles (e.g., HLA-B27) are enriched among human immunodeficiency virus type 1 (HIV-1)-infected individuals who suppress viremia without treatment (termed elite controllers [ECs]). Likewise,Mamu-B*8 expression also predisposes rhesusmacaques to control simian immunodeficiency virus (SIV) replication. Given the similarities between Mamu-B*8 and HLA-B*27, SIV-infected Mamu-B *8+ animals provide a model to investigate HLA-B*27-mediated elite control.We have recently shown that vaccination with three immunodominantMamu-B*8-re-stricted epitopes (Vif RL8, Vif RL9, and Nef RL10) increased the incidence of elite control inMamu-B*8± macaques after challenge with the pathogenic SIV mac239 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 amonotypic vaccine-induced Nef RL10-specific CD8+ T-cell re-sponse would facilitate the development of elite control inMamu-B*8+ animals following repeated intrarectal challenges with SIVmac239. To test this, we vaccinatedMamu-B*8+ animals with nef inserts in which Nef RL10 was either left intact (group 1) or disrupted bymutations (group 2). Althoughmonkeys in both groupsmounted Nef-specific cellular responses, only those in group 1 developed Nef RL10-specific CD8+ T cells. These vaccine-induced effectormemory 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 inMamu-B*8± macaques.

Original languageEnglish (US)
Pages (from-to)10802-10820
Number of pages19
JournalJournal of virology
Volume89
Issue number21
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8<sup>+</sup> T-Cell Responses Focused on a Single Nef Epitope Select for Escape Variants Shortly after Infection'. Together they form a unique fingerprint.

Cite this