Ragon Institute of MGH, MIT and Harvard, Boston, MA 02114, USA.
Immunity. 2012 Sep 21;37(3):426-40. doi: 10.1016/j.immuni.2012.09.005.
Successful vaccine development for infectious diseases has largely been achieved in settings where natural immunity to the pathogen results in clearance in at least some individuals. HIV presents an additional challenge in that natural clearance of infection does not occur, and the correlates of immune protection are still uncertain. However, partial control of viremia and markedly different outcomes of disease are observed in HIV-infected persons. Here, we examine the antiviral mechanisms implicated by one variable that has been consistently associated with extremes of outcome, namely HLA class I alleles, and in particular HLA-B, and examine the mechanisms by which this modulation is likely to occur and the impact of these interactions on evolution of the virus and the host. Studies to date provide evidence for both HLA-dependent and epitope-dependent influences on viral control and viral evolution and have important implications for the continued quest for an effective HIV vaccine.
传染病疫苗的成功开发在很大程度上是在病原体自然免疫导致至少一些个体清除的情况下实现的。HIV 带来了额外的挑战,因为感染不会自然清除,免疫保护的相关性仍然不确定。然而,在感染 HIV 的人中可以观察到病毒血症的部分控制和疾病结果的显著差异。在这里,我们研究了一个与结果极端相关的变量所涉及的抗病毒机制,即 HLA Ⅰ类等位基因,特别是 HLA-B,并研究了这种调节可能发生的机制以及这些相互作用对病毒和宿主进化的影响。迄今为止的研究为 HLA 依赖性和表位依赖性对病毒控制和病毒进化的影响提供了证据,对继续寻求有效的 HIV 疫苗具有重要意义。