| Literature DB >> 30936489 |
Qihui Wang1,2,3, Tong Ma1,4, Yan Wu2,5, Zhihai Chen6, Hui Zeng7, Zhou Tong1, Feng Gao8, Jianxun Qi9, Zhennan Zhao9, Yan Chai9, Huabing Yang1,4, Gary Wong10,11, Yuhai Bi9, Lili Wu1, Rui Shi1, Mi Yang1, Jian Song9, Haihai Jiang9,12, Zhiqiang An3, Junzhi Wang13, Tilahun D Yilma14,15, Yi Shi2,9,16, William J Liu17, Mifang Liang17, Chuan Qin18, George F Gao19,20,21,22,23,24,25, Jinghua Yan26,27,28,29,30.
Abstract
Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.Entities:
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Year: 2019 PMID： 30936489 DOI： 10.1038/s41564-019-0411-z
Source DB: PubMed Journal: Nat Microbiol ISSN： 2058-5276 Impact factor: 17.745