Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope.
Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope.
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DOI：
10.1016/j.cell.2021.07.006
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发表时间：
2021-08-19
期刊：
影响因子：
64.5
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Kim AS;Kafai NM;Winkler ES;Gilliland TC Jr;Cottle EL;Earnest JT;Jethva PN;Kaplonek P;Shah AP;Fong RH;Davidson E;Malonis RJ;Quiroz JA;Williamson LE;Vang L;Mack M;Crowe JE Jr;Doranz BJ;Lai JR;Alter G;Gross ML;Klimstra WB;Fremont DH;Diamond MS
甲病毒是一种新出现的蚊子传播的病原体，可导致人类肌肉骨骼和神经系统疾病。尽管已经描述了抑制单个甲病毒的中和抗体，但是尚未报道保护免受致关节炎和脑炎甲病毒两者的广泛反应性抗体。在这里，我们确定了DC2.112和DC2.315，这两种泛保护性但中和性差的人单克隆抗体（mAb），它们与感染致关节炎和脑炎甲病毒的细胞表面上的病毒抗原结合。这些mAb与融合肽附近和融合肽内的E1蛋白的结构域II中的保守表位接合。用DC2.112或DC2.315治疗通过多种机制保护小鼠免受致关节炎（基孔肯雅和马亚罗）和脑炎（委内瑞拉、东方和西方马脑炎）病毒的感染，包括抑制病毒外出和单核细胞依赖性Fc效应子功能。这些发现定义了一种被弱中和但保护性抗体识别的保守表位，该表位可以被靶向用于泛甲病毒免疫治疗和疫苗设计。Kim等人鉴定了人单克隆抗体，其通过病毒外出抑制和单核细胞依赖性抗体效应子功能在小鼠中保护免受致关节炎（基孔肯雅和Mayaro）和脑炎（委内瑞拉、东部和西部马脑炎）甲病毒的感染。这些抗体映射到E1蛋白中高度保守的融合环表位。
Alphaviruses are emerging, mosquito-transmitted pathogens that cause musculoskeletal and neurological disease in humans. Although neutralizing antibodies that inhibit individual alphaviruses have been described, broadly-reactive antibodies that protect against both arthritogenic and encephalitic alphaviruses have not been reported. Here, we identify DC2.112 and DC2.315, two pan-protective yet poorly neutralizing human monoclonal antibodies (mAbs) that avidly bind to viral antigen on the surface of cells infected with arthritogenic and encephalitic alphaviruses. These mAbs engage a conserved epitope in domain II of the E1 protein proximal to and within the fusion peptide. Treatment with DC2.112 or DC2.315 protects mice against infection by both arthritogenic (chikungunya and Mayaro) and encephalitic (Venezuelan, Eastern, and Western equine encephalitis) viruses through multiple mechanisms including inhibition of viral egress and monocyte-dependent Fc effector functions. These findings define a conserved epitope recognized by weakly neutralizing yet protective antibodies that could be targeted for pan-alphavirus immunotherapy and vaccine design. Kim et al. identify human monoclonal antibodies that protect in mice against infection by arthritogenic (chikungunya and Mayaro) and encephalitic (Venezuelan, Eastern, and Western equine encephalitis) alphaviruses through viral egress inhibition and monocyte-dependent antibody effector functions. These antibodies map to the highly conserved fusion loop epitope in the E1 protein.
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影响因子：
3.8
作者：
Hunt, Ann R.;Frederickson, Shana;Roehrig, John T.
通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
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作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
影响因子：
3.8
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通讯作者：
Streblow DN
影响因子：
8.8
作者：
Hasan, S. Saif;Sun, Chengqun;Rossmann, Michael G.
通讯作者：
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