Department of Biochemistry, University of Washington, Seattle, USA.
Curr Opin HIV AIDS. 2009 Sep;4(5):431-40. doi: 10.1097/COH.0b013e32832e6184.
We review structural information on the native HIV envelope trimer and the known epitopes for broadly neutralizing antibodies and discuss how this structural information should guide the design of more effective immunogens.
Recent epitope mapping of HIV-positive sera demonstrates that the immune system is able to mount a potent and broadly neutralizing antibody response against conserved elements of the HIV envelope. The structure of trimeric envelope spikes on intact HIV-1 virions (the target of neutralizing antibodies) was determined at low resolution using cryo-electron tomography. Fitting high-resolution crystal structures of monomeric gp120 complexed with different neutralizing ligands into the cryo-electron density maps provides useful models for the native virion trimer and for mechanisms of neutralization.
So far, all attempts to elicit broadly neutralizing antibodies against HIV by immunization have failed. Recent structural information on the virion-associated HIV envelope spike and of the precise interaction of broadly neutralizing mAbs with their epitopes clarifies the steric and geometric constraints faced by antibodies targeting conserved HIV epitopes. Implications for vaccine design are discussed.
我们回顾了天然 HIV 包膜三聚体的结构信息和已知的广谱中和抗体表位，并讨论了这些结构信息应如何指导更有效免疫原的设计。
最近对 HIV 阳性血清的表位作图表明，免疫系统能够针对 HIV 包膜的保守元件产生强大的广谱中和抗体反应。使用冷冻电镜断层扫描术以低分辨率测定了完整 HIV-1 病毒颗粒（中和抗体的靶标）上三聚体包膜刺突的结构。将高分辨率的单体 gp120 与不同中和配体复合物的晶体结构拟合到冷冻电镜密度图中，为天然病毒三聚体和中和机制提供了有用的模型。
到目前为止，通过免疫接种来诱导针对 HIV 的广谱中和抗体的所有尝试都失败了。最近关于病毒相关 HIV 包膜刺突的结构信息以及广谱中和 mAb 与其表位的确切相互作用，阐明了针对保守 HIV 表位的抗体所面临的空间和几何限制。讨论了对疫苗设计的影响。
