为了了解病毒感染和宿主免疫,研究人员确定了NiV G同源四聚体与nAH1.3广泛中和抗体Fab片段复合物的低温电子显微镜结构。他们发现,两种非重叠 G 特异性抗体的混合物可协同中和 NiV 和 HeV,并限制逃逸突变体的出现。用 NiV G 对猕猴进行疫苗接种所引发的多克隆血清抗体反应的分析表明,受体结合头部结构域是免疫显性的。 这些结果为针对这些致命病原体实施多管齐下的治疗策略铺平了道路。
据介绍,尼帕病毒 (NiV) 和亨德拉病毒 (HeV) 是导致脑炎和呼吸道疾病暴发的人畜共患亨尼帕病毒 (HNV)。 HNV 进入宿主细胞需要附着 (G) 和融合 (F) 糖蛋白,它们是抗体应答的主要靶标。
附:英文原文
Title: Architecture and antigenicity of the Nipah virus attachment glycoprotein
Author: Zhaoqian Wang, Moushimi Amaya, Amin Addetia, Ha V. Dang, Gabriella Reggiano, Lianying Yan, Andrew C. Hickey, Frank DiMaio, Christopher C. Broder, David Veesler
Issue&Volume: 2022-03-03
Abstract: Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness. HNVs entry into host cells requires the attachment (G) and fusion (F) glycoproteins which are the main targets of antibody responses. To understand viral infection and host immunity, we determined a cryo-electron microscopy structure of the NiV G homotetrameric ectodomain in complex with the nAH1.3 broadly neutralizing antibody Fab fragment. We show that a cocktail of two non-overlapping G-specific antibodies neutralizes NiV and HeV synergistically and limits the emergence of escape mutants. Analysis of polyclonal serum antibody responses elicited by vaccination of macaques with NiV G indicates that the receptor-binding head domain is immunodominant. These results pave the way for implementing multi-pronged therapeutic strategies against these deadly pathogens.
DOI: abm5561
Source: https://www.science.org/doi/10.1126/science.abm5561