Challenges for structure-based HIV vaccine design
Challenges for structure-based HIV vaccine design
复制标题
DOI：
10.1097/coh.0b013e32832e6184
复制
发表时间：
2009-09-01
影响因子：
4.1
通讯作者：
Stamatatos, Leonidas
中科院分区：
文献类型：
--
作者：
Schief, William R.;Ban, Yih-En Andrew;Stamatatos, Leonidas
审查的目的我们审查的结构信息的原生HIV包膜三聚体和广泛中和抗体的已知表位，并讨论如何这种结构信息应指导设计更有效的immunogen.Recent findingsRecent抗原决定簇的HIV阳性血清表明，免疫系统是能够安装一个强大的和广泛的中和抗体反应对保守的元素的HIV包膜。完整的HIV-1病毒体（中和抗体的靶点）上的三聚体包膜刺突的结构使用冷冻电子断层扫描在低分辨率下测定。拟合高分辨率的晶体结构的单体gp 120与不同的中和配体复杂的冷冻电子密度图提供了有用的模型为本地病毒体三聚体和机制的neutralization.SummarySo迄今为止，所有的尝试，以引起广泛的中和抗体对HIV的免疫接种都失败了。最近关于病毒体相关HIV包膜刺突和广泛中和mAb与其表位的精确相互作用的结构信息阐明了靶向保守HIV表位的抗体所面临的空间和几何约束。疫苗设计的影响进行了讨论。
Purpose of reviewWe 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 findingsRecent 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.SummarySo 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.