气候变化领域集成服务门户(CCPortal): Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition

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DOI	10.1073/pnas.2025642118
	Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition
	Chapman N.S.; Zhao H.; Kose N.; Westover J.B.; Kalveram B.; Bombardi R.; Rodriguez J.; Sutton R.; Genualdi J.; LaBeaud A.D.; Mutuku F.M.; Pittman P.R.; Freiberg A.N.; Gowen B.B.; Fremont D.H.; Crowe Jr J.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Rift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here,we report the isolation of a panel of monoclonal antibodies (mAbs) from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins. The Gn-specific mAbs and two mAbs that do not recognize either monomeric Gc or Gn alone but recognized the hetero-oligomer glycoprotein complex (Gc+Gn) when Gc and Gn were coexpressed exhibited potent neutralizing activities in vitro, while Gc-specific mAbs exhibited relatively lower neutralizing capacity. The two Gc+Gn-specific mAbs and the Gn domain A-specific mAbs inhibited RVFV fusion to cells, suggesting that mAbs can inhibit the exposure of the fusion loop in Gc, a class II fusion protein, and thus prevent fusion by an indirect mechanism without direct fusion loop contact. Competition-binding analysis with coexpressed Gc/Gn and mutagenesis library screening indicated that these mAbs recognize four major antigenic sites, with two sites of vulnerability for neutralization on Gn. In experimental models of infection in mice, representative mAbs recognizing three of the antigenic sites reduced morbidity and mortality when used at a low dose in both prophylactic and therapeutic settings. This study identifies multiple candidate mAbs that may be suitable for use in humans against RVFV infection and highlights fusion inhibition against bunyaviruses as a potential contributor to potent antibodymediated neutralization. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adaptive immunity; Antibodies; Monoclonal; Phlebovirus; Rift Valley fever virus; Virus internalization
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180009
作者单位	Department of Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO 63110, United States; Department of Animal Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, United States; Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, United States; Department of Pediatrics, Division of Infectious Diseases, Stanford University, School of Medicine, Stanford, CA 94305, United States; Department of Environment and Health Sciences, Technical University of Mombasa, Mombasa, Kenya; Medical Research and Material Command, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, United States; Center for Biodefense and Emerging Infectious Diseases, University of T...
推荐引用方式 GB/T 7714	Chapman N.S.,Zhao H.,Kose N.,et al. Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition[J],2021,118(14).
APA	Chapman N.S..,Zhao H..,Kose N..,Westover J.B..,Kalveram B..,...&Crowe Jr J.E..(2021).Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Chapman N.S.,et al."Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).