HIV VACCINE RATIONALE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 目前在HIV-1疫苗领域的争论涉及免疫缺陷病毒引起保护性反应的能力。一种观点认为，HIV-1重复感染在健康个体中很常见，因为病毒逃避了传统的免疫监视，这是疫苗设计的一个严重障碍。相反的论点是，防止双重感染是重要的，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SHIV KU-1-d（SHIV KU-1的衍生物）的静脉注射，并休息了10个月。感染在两种动物中引起不同的中和抗体活性。然后将动物暴露于SHIV 89.6P（静脉注射），携带相对于疫苗株的异源包膜蛋白的病毒。通过病毒载量和CD 4 + T细胞测量监测感染。所有对照动物均被感染，大多数死于疾病。相比之下，在试验猴中对重复感染的保护具有统计学显著性;在6个月的观察期内，一只动物在任何时间点均未显示重复感染的证据，第二只动物仅在一个时间点显示病毒的证据。两只动物均未出现疾病迹象。也许这种保护性状态可以作为HIV-1疫苗开发的“黄金标准”，因为类似程度的对人类免疫缺陷病毒感染的保护是非常理想的。

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.