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.
ASJC Scopus subject areas
- Insect Science