Neutralizing antibodies elicited by Nipah virus G-head nanoparticle target diverse sites and inhibit receptor binding and fusion
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Le résumé fourni par la source
Abstract Nipah virus (NiV) and Hendra virus (HeV), two highly pathogenic Henipaviruses (HNVs), pose a significant public health threat. The attachment glycoprotein (G) plays a crucial role in viral attachment and entry, making it an attractive target for vaccine and therapeutic antibody development. However, the antigenic landscape and neutralization sensitivity of the G protein remain poorly defined. Here, we systematically characterize 27 monoclonal antibodies (mAbs) elicited by NiV G head (G H ) nanoparticle-immunized mice. Among these, 25 mAbs exhibit neutralizing activity against two major NiV strains, NiV-Malaysia and NiV-Bangladesh, with five mAbs also cross-inhibiting HeV infection. Although all mAbs target G H , they inhibit viral infection through distinct mechanisms, either by blocking receptor ephrin-B2 engagement with the G protein or by preventing viral membrane fusion. Notably, mAbs from two distinct groups conferred complete protection to hamsters against lethal NiV-Malaysia infection. Structural analysis of NiV G H in complex with four representative Fabs reveals four non-overlapping epitopes, including two novel antigenic sites and one shared protective epitope identified across species. Our study provides a comprehensive map of the antigenic determinants of NiV G H , elucidates the relationship between epitopes, neutralization mechanisms, and protection, and offers new insights and opportunities for antibody-based therapies and vaccine development. Highlights Most mAbs induced in G head nanoparticle-immunized mice are potent neutralizers MAbs recognizing the G head block receptor binding or viral fusion Structural analysis shows mAbs target four distinct epitopes on G head protein Receptor competition site on G head is a shared protective antigenic site in human and multiple animals
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Neutralizing antibodies elicited by Nipah virus G-head nanoparticle target diverse sites and inhibit receptor binding and fusion
- Date Crossref
- 19/02/2025
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Wuhan University pays non établi dans la noticeUniversité ou école supérieure
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Wuhan Institute of Virology Center for Biosafety Mega-Science pays non établi dans la noticeStructure de recherche
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Chinese Academy of Sciences pays non établi dans la noticeOrganisme public
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University of Science and Technology of China Department of Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
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Anhui Provincial Center for Disease Control and Prevention pays non établi dans la noticeOrganisme public
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College of Life Sciences State Key Laboratory of Virology and Biosafety pays non établi dans la noticeUniversité ou école supérieure
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State Key Laboratory of Virology and Biosafety pays non établi dans la noticeStructure de recherche
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Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases pays non établi dans la noticeStructure de recherche
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Hubei Jiangxia Laboratory pays non établi dans la noticeStructure de recherche
Wuhan University, Center for Biosafety Mega-Science — Wuhan Institute of Virology et Chinese Academy of Sciences, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.