Stratov Ivan, DeRose Robert, Purcell Damian F J, Kent Stephen J
Department of Immunology and Microbiology, University of Melbourne, Victoria 3010, Australia.
Curr Drug Targets. 2004 Jan;5(1):71-88. doi: 10.2174/1389450043490686.
The HIV/AIDS pandemic is a global emergency and a preventive HIV vaccine is urgently needed. HIV has, however, proved a difficult pathogen to vaccinate against. This is largely because HIV has a very high mutation rate and can escape immune responses, it has a latent stage where it can rest silently integrated into host DNA, and neutralising antibodies that can neutralise diverse field strains have so far proved difficult to induce. There is however, considerable evidence now that HIV-specific CD4 and CD8 T cells can provide partial control of HIV replication and delay or prevent disease. Technologies to quantify and analyse HIV-specific T cells have advanced recently, and in particular ELISpot, intracellular cytokine staining and tetramer studies have provided clear analyses of the ability of HIV vaccines to induce T cell responses. The use of pools of overlapping HIV peptides as in vitro antigens has also provided a standardised reagent for accurate measurement of T cell responses. HIV protein vaccines have not induced broad neutralising antibodies or T cell responses and failed to protect humans in the only phase III efficacy trial yet completed. Viral vectors, such as canarypox, engineered to express HIV genes, have induced HIV-specific CD8 T cell responses in a minority of subjects in phase II trials and are proceeding to human efficacy trials. Currently, the most effective method of inducing CD8+ CTL immunity in non-human primates utilises priming with naked plasmid DNA and then boosting with recombinant viral vectors both encoding various parts of the HIV genome. Such vaccines have induced non-sterilising immunity to virulent Simian/Human immunodeficiency virus exposure in macaques and have entered phase I trials. Multiple other approaches are also being evaluated in what has become a global effort for a vaccine to prevent AIDS. Although an HIV vaccine is still a long way off, there is reason to be optimistic that a vaccine to prevent AIDS will eventually be developed.
艾滋病毒/艾滋病大流行是一场全球紧急情况，迫切需要一种预防性艾滋病毒疫苗。然而，事实证明，艾滋病毒是一种难以通过接种疫苗预防的病原体。这主要是因为艾滋病毒的突变率非常高，能够逃避免疫反应，它有一个潜伏期，可以静静地潜伏在宿主DNA中，而且迄今为止，很难诱导出能够中和多种野外毒株的中和抗体。然而，现在有大量证据表明，艾滋病毒特异性CD4和CD8 T细胞可以部分控制艾滋病毒的复制，延缓或预防疾病。量化和分析艾滋病毒特异性T细胞的技术最近有了进展，特别是酶联免疫斑点法、细胞内细胞因子染色和四聚体研究已经对艾滋病毒疫苗诱导T细胞反应的能力进行了清晰的分析。使用重叠艾滋病毒肽库作为体外抗原也为准确测量T细胞反应提供了标准化试剂。艾滋病毒蛋白疫苗尚未诱导出广泛的中和抗体或T细胞反应，并且在唯一一项已完成的III期疗效试验中未能保护人类。经基因工程改造以表达艾滋病毒基因的病毒载体，如金丝雀痘病毒，在II期试验中已在少数受试者中诱导出艾滋病毒特异性CD8 T细胞反应，目前正在进行人体疗效试验。目前，在非人类灵长类动物中诱导CD8+ CTL免疫的最有效方法是先用裸质粒DNA进行启动，然后用编码艾滋病毒基因组各个部分的重组病毒载体进行加强免疫。这类疫苗已在猕猴中诱导出对强毒性猿猴/人类免疫缺陷病毒暴露的非灭菌免疫力，并已进入I期试验。在全球预防艾滋病疫苗的努力中，还在评估多种其他方法。尽管距离研发出艾滋病毒疫苗仍有很长的路要走，但有理由乐观地认为，最终将会研发出预防艾滋病的疫苗。
