美国华盛顿大学医学院Michael S. Diamond研究团队发现，泛保护性的抗阿尔法病毒人类抗体靶向一个保守的E1蛋白表位。该研究于2021年8月19日发表于国际一流学术期刊《细胞》。
研究人员确定了DC2.112和DC2.315这两种泛保护性但中和性较差的人类单克隆抗体（mAb），它们能与感染了关节炎和脑炎阿尔法病毒的细胞表面的病毒抗原结合。这些mAb与E1蛋白结构域II中的一个保守表位相接触，该表位在融合肽的近端和内部。用DC2.112或DC2.315治疗可通过多种机制保护小鼠免受致关节炎（基孔肯雅病毒和马亚罗病毒）和脑炎（委内瑞拉、东部和西部马脑炎）阿尔法病毒的感染，包括抑制病毒的排出和单核细胞依赖的Fc效应功能。这些发现确定了一个保守的表位，该表位被弱中和但具有保护作用的抗体识别，可作为泛阿尔法病毒免疫疗法和疫苗设计的靶标。
据了解，阿尔法病毒是新出现的、由蚊子传播的病原体，会引起人类的肌肉骨骼和神经系统疾病。虽然已经描述了抑制个别阿尔法病毒的中和抗体，但还没有报道过对关节炎和脑炎阿尔法病毒都有保护作用的广泛反应性抗体。
附：英文原文
Title: Pan-protective anti-alphavirus human antibodies target a conserved E1 protein epitope
Author: Arthur S. Kim, Natasha M. Kafai, Emma S. Winkler, Theron C. Gilliland, Emily L. Cottle, James T. Earnest, Prashant N. Jethva, Paulina Kaplonek, Aadit P. Shah, Rachel H. Fong, Edgar Davidson, Ryan J. Malonis, Jose A. Quiroz, Lauren E. Williamson, Lo Vang, Matthias Mack, James E. Crowe, Benjamin J. Doranz, Jonathan R. Lai, Galit Alter, Michael L. Gross, William B. Klimstra, Daved H. Fremont, Michael S. Diamond
Issue&Volume: 2021/08/19
Abstract: Alphaviruses are emerging, mosquito-transmitted pathogens that cause musculoskeletaland neurological disease in humans. Although neutralizing antibodies that inhibitindividual alphaviruses have been described, broadly reactive antibodies that protectagainst both arthritogenic and encephalitic alphaviruses have not been reported. Here,we identify DC2.112 and DC2.315, two pan-protective yet poorly neutralizing humanmonoclonal antibodies (mAbs) that avidly bind to viral antigen on the surface of cellsinfected with arthritogenic and encephalitic alphaviruses. These mAbs engage a conservedepitope 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 equineencephalitis) alphaviruses through multiple mechanisms, including inhibition of viralegress and monocyte-dependent Fc effector functions. These findings define a conservedepitope recognized by weakly neutralizing yet protective antibodies that could betargeted for pan-alphavirus immunotherapy and vaccine design.
DOI: 10.1016/j.cell.2021.07.006
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00832-1