IMMUNOLOGIC STUDIES--HIV NEUTRALIZING ANTIBODIES AND VACCINE DEVELOPMENT

在研究免疫监视机制时， 人类免疫缺陷病毒（HIV-1）感染，我们有 集中研究HIV-1中和抗体， 1985年发现。 在一项有限的调查中，HIV-1感染者 具有高几何平均中和抗体滴度， 疾病表现。 随后，在儿科艾滋病病例中， 中和抗体与稳定临床状态的关系， 而不是一个穷人，被观察到。 回顾性 对HIV-1血清阳性地中海贫血患者进行调查， 中和抗体也与更好的临床 结果。 正在进行的HIV-1的长期前瞻性研究- 受感染的个体旨在阐明任何保护作用， HIV-1中和抗体。 在相关研究中， HIV-1包膜异质性对HIV-1基因的诱导和功能的影响 中和抗体正在研究中。 一种HIV-1变异病毒 是通过传播和繁殖克隆病毒获得的 在中和血清的存在下分离，表明 型特异性中和抗体自然产生。 是否 这种抗体可以引起突变病毒的免疫选择 在体内产生并影响疾病进展仍有待进一步研究。 测定 对变异体的遗传分析表明， 微小的变化是其中和性丧失的原因。 进一步的研究将确定重要的表位。 其他 鉴定中和表位的方法包括使用 病毒GP 120的中和性单克隆抗体 在 合作研究，各种潜在疫苗的能力 制备以引发高滴度、广泛反应性、中和 正在检查抗体。

In studying immune surveillance mechanisms operative following human immunodeficiency virus (HIV-1) infection, we have concentrated on HIV-1 neutralizing antibodies which we first detected in 1985. In a limited survey, HIV-1-infected individuals with high geometric mean neutralizing antibody titers had lesser disease manifestations. Subsequently in pediatric AIDS cases, a relationship of neutralizing antibodies and a stable clinical state, as opposed to a poor one, was observed. In a retrospective investigation of HIV-1-sero-positive thalassemia patients, neutralizing antibodies also were associated with a better clinical outcome. Ongoing long-term prospective studies of HIV-1- infected individuals are aimed at elucidating any protective role of HIV-1 neutralizing antibodies. In related studies, the effect of HIV-1 envelope heterogeneity on the elicitation and function of neutralizing antibodies is being pursued. An HIV-1 variant virus was obtained by transmitting and propagating a cloned virus isolate in the presence of a neutralizing serum, indicating that type-specific neutralizing antibodies occur naturally. Whether such antibodies can cause immune selection of mutant viruses arising in vivo and influence disease progression remains to be determined. Genetic analysis of the variant has shown that a minor change was responsible for its loss of neutralizability. Further studies will pinpoint important epitopes. Other approaches for identification of neutralizing epitopes include use of a neutralizing monoclonal antibody to the viral gp120. In collaborative studies, the ability of various potential vaccine preparations to elicit high-titer, broadly reactive, neutralizing antibodies is being examined.