McKeating J A, Balfe P
University of Reading, School of Animal and Microbial Sciences, Whiteknights, UK.
Immunol Lett. 1999 Jan;65(1-2):63-70. doi: 10.1016/s0165-2478(98)00126-6.
The study of the immunological defects which arise from HIV infection has led to a deeper understanding both of the normal immune system and of the mechanisms by which it is damaged in disease. The interactions between viral and host factors during the early stages of HIV infection leads to a post-seroconversion steady state or 'set point' of viral RNA load, which has been shown to be a prognostic marker for subsequent progression rates, further underlining the important role of early immunological responses in the disease process. The changing immune response during the course of infection, together with the changing patterns of antigenicity and tropism leads to a complex series of evolutionary interactions which can be monitored as a series of changes in the properties of the virus over time. Furthermore, significant differences may be seen between the antigenicity of viruses adapted to grow in tissue culture and viruses cultured only briefly in primary cells, and also between the antigenicity of monomeric and oligomeric subunit immunogens. The immunodominant, highly polymorphic and rapidly changing envelope glycoproteins of HIV remains the single biggest target for the design of successful candidate vaccines. The recent crystallisation of one HIV envelope, the proven existence of functionally conserved neutralisation targets and our increasing knowledge of the behaviour of the envelope glycoprotein in vivo offers the possibility that the next generation of vaccine candidates will have a far higher chance of success than has currently been achieved.
对由HIV感染引起的免疫缺陷的研究，使人们对正常免疫系统以及疾病中免疫系统受损机制有了更深入的了解。HIV感染早期病毒与宿主因素之间的相互作用导致病毒RNA载量在血清转化后达到稳定状态或“设定点”，这已被证明是后续疾病进展速度的预后标志物，进一步强调了早期免疫反应在疾病进程中的重要作用。感染过程中不断变化的免疫反应，以及抗原性和嗜性的变化模式，导致了一系列复杂的进化相互作用，这些相互作用可以作为病毒特性随时间的一系列变化来监测。此外，适应在组织培养中生长的病毒与仅在原代细胞中短暂培养的病毒之间，以及单体和寡聚体亚基免疫原的抗原性之间可能会出现显著差异。HIV免疫显性、高度多态且快速变化的包膜糖蛋白仍然是成功候选疫苗设计的最大单一靶点。最近一种HIV包膜的结晶、功能保守中和靶点的证实存在以及我们对包膜糖蛋白在体内行为的日益了解，使得下一代候选疫苗成功的可能性比目前已取得的成果要高得多。
