Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies
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 curren...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/81743 |
| _version_ | 1797839404077678592 |
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| author | Taylor B Engdahl Elad Binshtein Rebecca L Brocato Natalia A Kuzmina Lucia M Principe Steven A Kwilas Robert K Kim Nathaniel S Chapman Monique S Porter Pablo Guardado-Calvo Félix A Rey Laura S Handal Summer M Diaz Irene A Zagol-Ikapitte Minh H Tran W Hayes McDonald Jens Meiler Joseph X Reidy Andrew Trivette Alexander Bukreyev Jay W Hooper James E Crowe |
| author_facet | Taylor B Engdahl Elad Binshtein Rebecca L Brocato Natalia A Kuzmina Lucia M Principe Steven A Kwilas Robert K Kim Nathaniel S Chapman Monique S Porter Pablo Guardado-Calvo Félix A Rey Laura S Handal Summer M Diaz Irene A Zagol-Ikapitte Minh H Tran W Hayes McDonald Jens Meiler Joseph X Reidy Andrew Trivette Alexander Bukreyev Jay W Hooper James E Crowe |
| author_sort | Taylor B Engdahl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:57:24Z |
| format | Article |
| id | doaj.art-8473aa7cf9fd4f6f8543805191bc6878 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T15:57:24Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-8473aa7cf9fd4f6f8543805191bc68782023-04-25T14:35:01ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.81743Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodiesTaylor B Engdahl0https://orcid.org/0000-0002-6280-4405Elad Binshtein1Rebecca L Brocato2Natalia A Kuzmina3Lucia M Principe4Steven A Kwilas5https://orcid.org/0000-0003-0383-3879Robert K Kim6Nathaniel S Chapman7Monique S Porter8Pablo Guardado-Calvo9https://orcid.org/0000-0001-7292-5270Félix A Rey10https://orcid.org/0000-0002-9953-7988Laura S Handal11Summer M Diaz12Irene A Zagol-Ikapitte13Minh H Tran14W Hayes McDonald15Jens Meiler16https://orcid.org/0000-0001-8945-193XJoseph X Reidy17Andrew Trivette18Alexander Bukreyev19https://orcid.org/0000-0002-0342-4824Jay W Hooper20James E Crowe21https://orcid.org/0000-0002-0049-1079Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United StatesVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United StatesDepartment of Pathology, The University of Texas Medical Branch at Galveston, Galveston, United States; Galveston National Laboratory, Galveston, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United StatesDepartment of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United StatesDepartment of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, United StatesInstitut Pasteur, Université Paris Cité, Paris, FranceInstitut Pasteur, Université Paris Cité, Paris, FranceVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United StatesVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United StatesDepartment of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United StatesDepartment of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, United StatesDepartment of Chemistry, Vanderbilt University, Nashville, United StatesVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United StatesVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, United StatesDepartment 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 StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases, Ft Detrick, United StatesDepartment 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 StatesHantaviruses 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.https://elifesciences.org/articles/81743hantavirusbunyavirusSin Nombre virusAndes virusHantaan virusantibody |
| spellingShingle | Taylor B Engdahl Elad Binshtein Rebecca L Brocato Natalia A Kuzmina Lucia M Principe Steven A Kwilas Robert K Kim Nathaniel S Chapman Monique S Porter Pablo Guardado-Calvo Félix A Rey Laura S Handal Summer M Diaz Irene A Zagol-Ikapitte Minh H Tran W Hayes McDonald Jens Meiler Joseph X Reidy Andrew Trivette Alexander Bukreyev Jay W Hooper James E Crowe Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies eLife hantavirus bunyavirus Sin Nombre virus Andes virus Hantaan virus antibody |
| title | Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies |
| title_full | Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies |
| title_fullStr | Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies |
| title_full_unstemmed | Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies |
| title_short | Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies |
| title_sort | antigenic mapping and functional characterization of human new world hantavirus neutralizing antibodies |
| topic | hantavirus bunyavirus Sin Nombre virus Andes virus Hantaan virus antibody |
| url | https://elifesciences.org/articles/81743 |
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