Vaccine-induced CD8~+ T cells control AIDS virus replication

摘要

Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus. Most of these elite controllers express the histocompatibility alkies HLA-B*57 or HLA-B*27 (ref. 3). These alleles remain by far the most robust associations with low concentrations of plasma virus, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate 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 control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 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 CD8~+ T-cell response against the Nef RL10 epitope (Nef amino acids 137-146) correlated significantly with reduced acute phase viraemia. 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 the 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.%表达Mamu-B*08分子(它与人白细胞抗原Classrn1分子HLA-B*27具有重要的结构相似性)的印度rn恒河猴对高致病性SIVmac239病毒有一定的控rn制能力。这个系统为携带艾滋病病毒(HIV)的rn人能够对该病毒有极好控制的罕见病例提供了rn一个模型。在这项研究中，Davla Watkins及其rn同事发现，由疫苗诱导产生的、被引导仅仅抵rn抗与Mamu-B*08结合的三个免疫显性T-细胞rn表位(Vif RL8、Vif RL9和Nef RL10)的CD8+Trn细胞，能够控制Mamu-B*