符合性抗原异质性作为HIV-1中和化中持续部分的原因
Philippe Colin1,2, Rajesh P Ringe1,3, Anila Yasmeen1
1Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, 1300 York Avenue, 62 , New York, NY, 10065, USA.
Retrovirology
|May 27, 2023
概括
对HIV-1的中和抗体 (NAbs) 显示出不同的有效性,不同的病毒包膜形式影响中和. 了解这些差异是开发更有效的抗体治疗HIV-1感染的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 中和抗体 (NAbs) 通过向病毒包膜糖蛋白 (Env) 来阻止HIV-1感染至关重要.
- NAbs的效力与亲和力有关,但在高抗体度下,感染力的持久部分仍然不太了解.
- 不同的HIV-1分离体对NAbs具有不同的敏感性,影响治疗策略.
研究的目的:
- 通过NAbs. 调查导致NAbs. 持续的HIV-1中和率的因素.
- 分析不同病毒包膜抗原形式对NAb疗效的影响.
- 阐明微分中和灵敏性的结构基础.
主要方法:
- 使用来自HIV-1分离物BG505和B41的伪病毒进行中和测定.
- 使用NAb结合珠的virion种群的耗尽.
- 表面等离子体共振来分析Env三元体-抗体相互作用.
- 结构分析以解释观察到的中和模式.
主要成果:
- 对具有特定NAbs (PGT151和PGT145) 的BG505和B41分离物观察到不同的持久分数.
- 在NAb消耗实验中,敏感度和持久分数的相互变化得到了证明.
- 表面等离子体共振揭示了与中和相关的Env三元体抗原性,动力学和静电学上的差异.
- 由PGT151中和B41的持久分数归因于由形状可塑性驱动的低静态度.
结论:
- 艾滋病毒-1 Env在病毒体上的明显的抗原形式影响NAb中和.
- 亲和净化方法可以偏向免疫原体呈现,影响NAb反应.
- 针对多个Env符合者的NAbs对于减少持久分数和提高整体中和效率至关重要.
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