Esparza J, Osmanov S, Heyward W L
Global Programme on AIDS, World Health Organization, Geneva, Switzerland.
Drugs. 1995 Nov;50(5):792-804. doi: 10.2165/00003495-199550050-00003.
The major conceptual problem for HIV vaccine development has been the lack of information on immune responses known to correlate with protection against HIV infection in humans. In this regard, studies on the natural history of HIV infection and AIDS, especially of people with apparent resistance to HIV infection and of patients with HIV infection who have long term survival without disease progression, may provide important information for vaccine development. In addition, a major concern for the development of broadly effective vaccines has been the extensive genetic variability which is characteristic of HIV. In spite of these unknowns, the first generation of HIV candidate vaccines has been developed and evaluated. HIV candidate vaccines based on the subunit recombinant envelope concept (gp120 or gp160) have been shown to protect chimpanzees from HIV infection on challenge, and have now been evaluated in humans in phase I and phase II trials. These products are well tolerated, and capable of inducing neutralising antibodies, but not cytotoxic T lymphocytes. A second vaccine concept, currently in phase I trials, is based on live recombinant vectors, especially using poxvirus vectors followed by boosting with subunit recombinant envelope vaccines. This concept is theoretically very attractive because preliminary data suggest that these vaccines induce both humoral and cell-mediated immunity. However, no published information is available on the ability of live recombinant vector vaccines to protect chimpanzees from HIV infection. The next step in HIV vaccine development is to proceed carefully to expanded phase II and phase III trials to assess the protective efficacy of these candidate vaccines in humans. These trials will be extremely complex from the logistical, scientific and ethical points of view, and will require close collaboration between clinical, basic science and behavioural researchers, national and international organisations, and the pharmaceutical industry.
艾滋病病毒疫苗研发的主要概念性问题在于，缺乏已知与人类预防艾滋病病毒感染相关的免疫反应信息。在这方面，对艾滋病病毒感染和艾滋病自然史的研究，特别是对明显具有艾滋病病毒感染抵抗力的人群以及长期存活且无疾病进展的艾滋病病毒感染患者的研究，可能为疫苗研发提供重要信息。此外，广泛有效的疫苗研发的一个主要担忧是艾滋病病毒具有广泛的基因变异性。尽管存在这些未知因素，但第一代艾滋病病毒候选疫苗已经研发并进行了评估。基于亚单位重组包膜概念（gp120或gp160）的艾滋病病毒候选疫苗已被证明能在黑猩猩受到攻击时保护它们免受艾滋病病毒感染，目前已在人类身上进行了一期和二期试验。这些产品耐受性良好，能够诱导中和抗体，但不能诱导细胞毒性T淋巴细胞。目前处于一期试验阶段的第二种疫苗概念基于活重组载体，特别是使用痘病毒载体，随后用亚单位重组包膜疫苗加强免疫。从理论上讲，这个概念非常有吸引力，因为初步数据表明这些疫苗能诱导体液免疫和细胞介导免疫。然而，关于活重组载体疫苗保护黑猩猩免受艾滋病病毒感染能力的公开信息尚无。艾滋病病毒疫苗研发的下一步是谨慎推进扩大的二期和三期试验，以评估这些候选疫苗对人类的保护效果。从后勤、科学和伦理角度来看，这些试验将极其复杂，需要临床、基础科学和行为研究人员、国家和国际组织以及制药行业之间密切合作。
