法国巴斯德研究所Felix A. Rey和美国德克萨斯大学奥斯汀分校Jason McLellan研究团队合作取得最新进展。他们揭示人抗体协同中和克里米亚-刚果出血热病毒 (CCHFV)的结构基础。2021年11月18日出版的《科学》杂志发表了这项成果。

他们描述了融合前 Gc（宿主中和抗体反应的主要靶标） 与两种中和抗体的抗原结合片段结合的结构，这些抗体在组合时表现出协同的、三聚体、融合后 Gc 结构。结构显示两个 Fab 协同作用阻止膜融合：一个靶向融合环，另一个阻止 Gc 三聚体的形成。这些结构还揭示了先前报道的抗 CCHFV 抗体的中和机制，为开发 CCHFV 特定的流行病预防医学对策提供了必不可少的分子基础。

据了解，CCHFV是最普遍的蜱传人畜共患病毒，人类病死率为 30%。目前，缺乏关于 CCHFV 膜融合糖蛋白Gc，以及抗体介导的中和机制的结构信息。

附：英文原文

Title: Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies

Author: Akaash K. Mishra, Jan Hellert, Natalia Freitas, Pablo Guardado-Calvo, Ahmed Haouz, J. Maximilian Fels, Daniel P. Maurer, Dafna M. Abelson, Zachary A. Bornholdt, Laura M. Walker, Kartik Chandran, Franois-Loc Cosset, Jason S. McLellan, Felix A. Rey

Issue&Volume: 2021-11-18

Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information on the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as on antibody-mediated neutralization mechanisms is lacking. We describe the structure of prefusion Gc bound to the antigen-binding fragments of two neutralizing antibodies that display synergy when combined, as well as to the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion: one targets the fusion loops, and the other blocks Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported anti-CCHFV antibodies, providing the molecular underpinnings essential for developing CCHFV-specific medical countermeasures for epidemic preparedness.

DOI: abl6502

Source: https://www.science.org/doi/10.1126/science.abl6502