Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits.
Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits.
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DOI：
10.1038/ncomms11544
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发表时间：
2016-05-10
影响因子：
16.6
通讯作者：
Garry RF
中科院分区：
文献类型：
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作者：
Robinson JE;Hastie KM;Cross RW;Yenni RE;Elliott DH;Rouelle JA;Kannadka CB;Smira AA;Garry CE;Bradley BT;Yu H;Shaffer JG;Boisen ML;Hartnett JN;Zandonatti MA;Rowland MM;Heinrich ML;Martínez-Sobrido L;Cheng B;de la Torre JC;Andersen KG;Goba A;Momoh M;Fullah M;Gbakie M;Kanneh L;Koroma VJ;Fonnie R;Jalloh SC;Kargbo B;Vandi MA;Gbetuwa M;Ikponmwosa O;Asogun DA;Okokhere PO;Follarin OA;Schieffelin JS;Pitts KR;Geisbert JB;Kulakoski PC;Wilson RB;Happi CT;Sabeti PC;Gevao SM;Khan SH;Grant DS;Geisbert TW;Saphire EO;Branco LM;Garry RF
拉沙热是一种严重的多系统疾病，通常有出血表现。自然感染的人类宿主识别的拉沙病毒（LASV）表面糖蛋白的表位尚未被鉴定或表征。我们从西非拉沙热幸存者的记忆 B 细胞中克隆了 113 种针对 LASV 糖蛋白特异性的人单克隆抗体 (mAb)。一半结合 GP2 融合亚基，四分之一识别 GP1 受体结合亚基，剩下的四分之一对组装的糖蛋白复合物具有特异性，需要 GP1 和 GP2 亚基进行识别。值得注意的是，在中和 LASV 的 16 种 mAb 中，13 种需要组装的糖蛋白复合物才能结合，而其余 3 种仅需要 GP1。与非中和性单克隆抗体相比，中和性单克隆抗体具有更高的结合亲和力，并且与种系祖细胞的差异更大。一些 mAb 可有效中和所有四种 LASV 谱系。这些来自 LASV 人单克隆抗体表征的见解将指导免疫治疗开发和疫苗设计策略。 拉沙病毒可引起出血热，目前尚无具体治疗方法。作者从拉沙病毒感染幸存者身上克隆了 113 种单克隆抗体，并表明大多数中和抗体靶向 GP1 和 GP2 病毒蛋白复合物。
Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design. Lassa virus can cause haemorrhagic fever for which no specific treatment currently exists. Here the authors have cloned 113 monoclonal antibodies from the survivors of Lassa infection and show that the majority of neutralizing antibodies target a complex of GP1 and GP2 viral proteins.