Neutralization Mechanisms Of Anti-HIV-1 Monoclonal Antibodies

缺乏中和抗体使HIV-1有别于大多数其他病毒病原体，并在很大程度上对HIV-1维持持续感染的能力负责。已分离出几种具有广泛中和作用的单抗。我们用X射线结晶学研究了广谱中和抗体的表位及其中和机制。特别是，我们检测了像VRC01这样的针对CD4结合位点的抗体，像PG9和PG16这样的四元抗体，以及像2F5这样的膜近端结合抗体。VRC01抗体特别有吸引力，因为它中和了90%以上的HIV-1循环分离株，并似乎在5-10%的HIV-1感染者中诱导出高滴度。第四代抗体也很有吸引力，因为一些组织估计这是最常见的广泛中和反应。

A lack of neutralizing antibodies distinguishes HIV-1 from most other viral pathogens and is responsible to a large degree for the ability of HIV-1 to maintain a persistent infection. A few monoclonal antibodies have been isolated that are broadly neutralizing. We have used X-ray crystallography to investigate the epitopes of broadly neutralizing antibodies and their mechanisms of neutralization. In particular, we have examined CD4-binding-site directed antibodies like VRC01, quaternary antibodies like PG9 and PG16, and membrane-proximal-binding antibodies like 2F5. The VRC01 antibody is particularly attractive as it neutralizes over 90% of circulating HIV-1 isolates and appears to be elicited in high titer in 5-10% of HIV-1 infected individuals. The quaternary antibodies are also attractive, as some groups estimate that this is the most commonly elicited broadly neutralizing response.