Antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies

  1. Taylor B Engdahl
  2. Elad Binshtein
  3. Rebecca L Brocato
  4. Natalia A Kuzmina
  5. Lucia M Principe
  6. Steven A Kwilas
  7. Robert K Kim
  8. Nathaniel S Chapman
  9. Monique S Porter
  10. Pablo Guardado-Calvo
  11. Félix A Rey
  12. Laura S Handal
  13. Summer M Diaz
  14. Irene A Zagol-Ikapitte
  15. Minh H Tran
  16. W Hayes McDonald
  17. Jens Meiler
  18. Joseph X Reidy
  19. Andrew Trivette
  20. Alexander Bukreyev
  21. Jay W Hooper  Is a corresponding author
  22. James E Crowe Jr.  Is a corresponding author
  1. Vanderbilt University, United States
  2. Vanderbilt University Medical Center, United States
  3. United States Army Medical Research Institute of Infectious Diseases, United States
  4. The University of Texas Medical Branch at Galveston, United States
  5. 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

  1. Taylor B Engdahl

    Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6280-4405
  2. Elad Binshtein

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  3. Rebecca L Brocato

    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States
    Competing interests
    No competing interests declared.
  4. Natalia A Kuzmina

    Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, United States
    Competing interests
    No competing interests declared.
  5. Lucia M Principe

    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States
    Competing interests
    No competing interests declared.
  6. Steven A Kwilas

    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0383-3879
  7. Robert K Kim

    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States
    Competing interests
    No competing interests declared.
  8. Nathaniel S Chapman

    Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  9. Monique S Porter

    Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  10. Pablo Guardado-Calvo

    Virology Department, Institut Pasteur, CNRS UMR 3569, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7292-5270
  11. Félix A Rey

    Virology Department, Institut Pasteur, CNRS UMR 3569, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9953-7988
  12. Laura S Handal

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  13. Summer M Diaz

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  14. Irene A Zagol-Ikapitte

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  15. Minh H Tran

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  16. W Hayes McDonald

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  17. Jens Meiler

    Department of Chemistry, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8945-193X
  18. Joseph X Reidy

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  19. Andrew Trivette

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    No competing interests declared.
  20. Alexander Bukreyev

    Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0342-4824
  21. Jay W Hooper

    Virology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United States
    For correspondence
    jay.w.hooper.civ@mail.mil
    Competing interests
    No competing interests declared.
  22. James E Crowe Jr.

    Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United States
    For correspondence
    james.crowe@vanderbilt.edu
    Competing interests
    James E Crowe, 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..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0049-1079

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.

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).

Reviewing Editor

  1. Arturo Casadevall, Johns Hopkins Bloomberg School of Public Health, United States

Version history

  1. Received: July 11, 2022
  2. Preprint posted: July 20, 2022 (view preprint)
  3. Accepted: March 27, 2023
  4. Accepted Manuscript published: March 27, 2023 (version 1)
  5. Version of Record published: April 19, 2023 (version 2)
  6. 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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  1. Taylor B Engdahl
  2. Elad Binshtein
  3. Rebecca L Brocato
  4. Natalia A Kuzmina
  5. Lucia M Principe
  6. Steven A Kwilas
  7. Robert K Kim
  8. Nathaniel S Chapman
  9. Monique S Porter
  10. Pablo Guardado-Calvo
  11. Félix A Rey
  12. Laura S Handal
  13. Summer M Diaz
  14. Irene A Zagol-Ikapitte
  15. Minh H Tran
  16. W Hayes McDonald
  17. Jens Meiler
  18. Joseph X Reidy
  19. Andrew Trivette
  20. Alexander Bukreyev
  21. Jay W Hooper
  22. James E Crowe Jr.
(2023)
Antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies
eLife 12:e81743.
https://doi.org/10.7554/eLife.81743

Share this article

https://doi.org/10.7554/eLife.81743

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