Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies.

Autor:	Engdahl TB; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States., Binshtein E; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States., Brocato RL; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States., Kuzmina NA; Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, United States.; Galveston National Laboratory, Galveston, United States., Principe LM; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States., Kwilas SA; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States., Kim RK; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States., Chapman NS; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States., Porter MS; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States., Guardado-Calvo P; Institut Pasteur, Université Paris Cité, Paris, France., Rey FA; Institut Pasteur, Université Paris Cité, Paris, France., Handal LS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States., Diaz SM; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States., Zagol-Ikapitte IA; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United States., Tran MH; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United States., McDonald WH; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United States., Meiler J; Department of Chemistry, Vanderbilt University, Nashville, United States., Reidy JX; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States., Trivette A; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States., Bukreyev A; Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, United States.; Galveston National Laboratory, Galveston, United States.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, United States., Hooper JW; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States., Crowe JE; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States.; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Mar 27; Vol. 12. Date of Electronic Publication: 2023 Mar 27.
DOI:	10.7554/eLife.81743
Abstrakt:	Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines. Competing Interests: TE, EB, RB, NK, LP, SK, RK, NC, MP, PG, FR, LH, SD, IZ, MT, WM, JM, JR, AT, AB, JH No competing interests declared, JC has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, GlaxoSmithKline and BTG International Inc, is a member of the Scientific Advisory Board of Meissa Vaccines, a former member of the Scientific Advisory Board of Gigagen (Grifols) and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study
Databáze:	MEDLINE
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