HIV VACCINE RATIONALE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前HIV-1疫苗领域的一场辩论涉及免疫缺陷病毒引发保护性反应的能力。一种说法是，HIV-1重复感染在健康人中很常见，因为病毒逃避了传统的免疫监测，这是疫苗设计的严重障碍。相反的论点是，对重复感染的保护是重要的，反映了一种强大的免疫反应，可以通过接种疫苗来预防疾病。在一项旨在解决这一争论的实验中，两只猕猴接受了SIV KU-1-d(SIV KU-1的衍生物)的静脉接种，并休息了10个月。感染可引起两种动物不同的中和抗体活性。动物随后被暴露于SIV 89.6P(静脉注射)，这是一种携带相对于疫苗毒株的异源包膜蛋白的病毒。通过病毒载量和CD4+T细胞测量来监测感染情况。所有对照动物都被感染，大多数人死于疾病。相比之下，对重复感染的保护在测试猴子中具有统计学意义；一只动物在任何时间点都没有显示出重复感染的证据，第二只动物在6个月的观察期内只在一个时间点显示出病毒的证据。两种动物都没有表现出疾病的迹象。也许这种保护状态可以作为HIV-1疫苗开发的“黄金标准”，因为对人类感染免疫缺陷病毒的类似程度的保护将是非常理想的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argument is that protection from superinfection is significant, reflecting a robust immune response that might be harnessed by vaccination to prevent disease. In an experiment designed to address the debate, two macaques received an I.V. inoculation with SHIV KU-1-d (a derivative of SHIV KU-1) and were rested for 10 months. Infection elicited diverse neutralizing antibody activities in both animals. Animals were then exposed to SHIV 89.6P (I.V.), a virus carrying a heterologous envelope protein relative to the vaccine strain. Infection was monitored by viral load and CD4+ T-cell measurements. All control animals were infected and most succumbed to disease. In contrast, protection from superinfection was statistically significant in test monkeys; one animal showed no evidence of superinfection at any time point and the second showed evidence of virus at only one time point over a 6-month observation period. Neither animal showed signs of disease. Perhaps this protective state may serve as a 'gold-standard' for HIV-1 vaccine development, as a similar degree of protection against immunodeficiency virus infections in humans would be much desired.