Antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies
- Vanderbilt University, United States
- Vanderbilt University Medical Center, United States
- United States Army Medical Research Institute of Infectious Diseases, United States
- The University of Texas Medical Branch at Galveston, United States
- Institut Pasteur, CNRS UMR 3569, France
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript.
Article and author information
Author details
Pablo Guardado-Calvo
Alexander Bukreyev
Funding
National Institute of Allergy and Infectious Diseases (5T32GM008320)
- Taylor B Engdahl
Military Infectious Diseases Program (MI210048)
- Jay W Hooper
NIH Office of the Director (S10 OD030292)
- James E Crowe Jr.
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arturo Casadevall, Johns Hopkins Bloomberg School of Public Health, United States
Ethics
Animal experimentation: Animal challenge studies were conducted in the ABSL-4 facility of the Galveston National Laboratory. The animal protocol for testing of mAbs in hamsters was approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Texas Medical Branch at Galveston (UTMB) (protocol #1912091).
Version history
- Received: July 11, 2022
- Preprint posted: July 20, 2022 (view preprint)
- Accepted: March 27, 2023
- Accepted Manuscript published: March 27, 2023 (version 1)
- Version of Record published: April 19, 2023 (version 2)
- Version of Record updated: April 25, 2023 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies
eLife 12:e81743.
https://doi.org/10.7554/eLife.81743
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