Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus

Qihui Wang, Tong Ma, Yan Wu, Zhihai Chen, Hui Zeng, Zhou Tong, Feng Gao, Jianxun Qi, Zhennan Zhao, Yan Chai, Huabing Yang, Gary Wong, Yuhai Bi, Lili Wu, Rui Shi, Mi Yang, Jian Song, Haihai Jiang, Zhiqiang An, Junzhi WangTilahun Yilma, Yi Shi, William J. Liu, Mifang Liang, Chuan Qin, George F. Gao, Jinghua Yan

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
JournalNature Microbiology
DOIs
StatePublished - Jan 1 2019

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Wang, Q., Ma, T., Wu, Y., Chen, Z., Zeng, H., Tong, Z., Gao, F., Qi, J., Zhao, Z., Chai, Y., Yang, H., Wong, G., Bi, Y., Wu, L., Shi, R., Yang, M., Song, J., Jiang, H., An, Z., ... Yan, J. (2019). Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus. Nature Microbiology. https://doi.org/10.1038/s41564-019-0411-z