Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection
Abstract Influenza remains a persistent global health challenge, largely due to the virus’ continuous antigenic drift and occasional shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanob...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55193-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544452719509504 |
|---|---|
| author | Zhao-Shan Chen Hsiang-Chi Huang Xiangkun Wang Karin Schön Yane Jia Michael Lebens Danica F. Besavilla Janarthan R. Murti Yanhong Ji Aishe A. Sarshad Guohua Deng Qiyun Zhu Davide Angeletti |
| author_facet | Zhao-Shan Chen Hsiang-Chi Huang Xiangkun Wang Karin Schön Yane Jia Michael Lebens Danica F. Besavilla Janarthan R. Murti Yanhong Ji Aishe A. Sarshad Guohua Deng Qiyun Zhu Davide Angeletti |
| author_sort | Zhao-Shan Chen |
| collection | DOAJ |
| description | Abstract Influenza remains a persistent global health challenge, largely due to the virus’ continuous antigenic drift and occasional shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolate and purify a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. The nanobody, named E10, exhibits broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrate that E10 specifically targets an epitope on HA head which is part of the conserved lateral patch and is highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicits cross-reactive antibodies and mediates partial protection from lethal viral challenge. Our data highlights the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies. |
| format | Article |
| id | doaj-art-a345da4a3f3348e1a172f75c5da730da |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a345da4a3f3348e1a172f75c5da730da2025-01-12T12:31:52ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55193-yInfluenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protectionZhao-Shan Chen0Hsiang-Chi Huang1Xiangkun Wang2Karin Schön3Yane Jia4Michael Lebens5Danica F. Besavilla6Janarthan R. Murti7Yanhong Ji8Aishe A. Sarshad9Guohua Deng10Qiyun Zhu11Davide Angeletti12State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of GothenburgState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgAbstract Influenza remains a persistent global health challenge, largely due to the virus’ continuous antigenic drift and occasional shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolate and purify a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. The nanobody, named E10, exhibits broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrate that E10 specifically targets an epitope on HA head which is part of the conserved lateral patch and is highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicits cross-reactive antibodies and mediates partial protection from lethal viral challenge. Our data highlights the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies.https://doi.org/10.1038/s41467-024-55193-y |
| spellingShingle | Zhao-Shan Chen Hsiang-Chi Huang Xiangkun Wang Karin Schön Yane Jia Michael Lebens Danica F. Besavilla Janarthan R. Murti Yanhong Ji Aishe A. Sarshad Guohua Deng Qiyun Zhu Davide Angeletti Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection Nature Communications |
| title | Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| title_full | Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| title_fullStr | Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| title_full_unstemmed | Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| title_short | Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| title_sort | influenza a virus h7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection |
| url | https://doi.org/10.1038/s41467-024-55193-y |
| work_keys_str_mv | AT zhaoshanchen influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT hsiangchihuang influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT xiangkunwang influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT karinschon influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT yanejia influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT michaellebens influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT danicafbesavilla influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT janarthanrmurti influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT yanhongji influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT aisheasarshad influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT guohuadeng influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT qiyunzhu influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection AT davideangeletti influenzaavirush7nanobodyrecognizesaconservedimmunodominantepitopeonhemagglutininheadandconfersheterosubtypicprotection |