Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus.
Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus.
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DOI：
10.1038/s41467-022-34923-0
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发表时间：
2022-11-26
影响因子：
16.6
通讯作者：
Pegan, Scott D.
中科院分区：
文献类型：
--
作者：
Durie, Ian A.;Tehrani, Zahra R.;Karaaslan, Elif;Sorvillo, Teresa E.;McGuire, Jack;Golden, Joseph W.;Welch, Stephen R.;Kainulainen, Markus H.;Harmon, Jessica R.;Mousa, Jarrod J.;Gonzalez, David;Enos, Suzanne;Koksal, Iftihar;Yilmaz, Gurdal;Karakoc, Hanife Nur;Hamidi, Sanaz;Albay, Cansu;Spengler, Jessica R.;Spiropoulou, Christina F.;Garrison, Aura R.;Sajadi, Mohammad M.;Bergeron, Eric;Pegan, Scott D.
克里米亚-刚果出血热病毒（CCHFV）是一种危及生命的疾病，死亡率高达40%。由于没有批准的医疗对策，CCHFV被认为是公共卫生优先代理。非中和性小鼠单克隆抗体（mAb）13 G8靶向CCHFV糖蛋白GP 38，并在预防性或治疗性给药时保护小鼠免受致死性CCHFV攻击。在这里，我们揭示了GP 38与人嵌合13 G8 mAb和新分离的CC 5 -17 mAb结合的结构。这些mAb以偏移的角度结合重叠表位。研究了c13 G8和CC 5 -17的广谱潜力以及使用它们对抗Aigai病毒（一种密切相关的内罗病毒）的实用性。结合研究表明，在Aigai病毒相应区域中存在非保守氨基酸阻止CCHFV mAb与Aigai病毒GP 38结合。这一信息，加上在体内的功效，铺平了道路，为未来的单克隆抗体治疗有效地对广泛的CCHFV菌株。目前没有批准的治疗克里米亚-刚果出血热病毒（CCHFV）感染的方法。在这项研究中，作者在结构上表征了保护性非中和小鼠和人抗体靶向的表位，并提供了对各种CCHFV毒株的广泛潜力的见解。
Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains. There are currently no approved treatments for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infection. In this study, the authors structurally characterize the epitope targeted by protective non-neutralizing mouse and human antibodies and provide insights into their broad range potential against various CCHFV strains.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
8.8
作者：
Earnest JT;Holmes AC;Basore K;Mack M;Fremont DH;Diamond MS
通讯作者：
Diamond MS
DOI：
10.1073/pnas.2200065119
发表时间：
2022-03-22
影响因子：
11.1
作者：
Foster SL;Woolsey C;Borisevich V;Agans KN;Prasad AN;Deer DJ;Geisbert JB;Dobias NS;Fenton KA;Cross RW;Geisbert TW
通讯作者：
Geisbert TW
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Bergeron, Eric;Vincent, Martin J.;Nichol, Stuart T.
通讯作者：
Nichol, Stuart T.