Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes
Abstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnA...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56496-4 |
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| author | Ting-Hui Lin Chang-Chun David Lee Monica L. Fernández-Quintero James A. Ferguson Julianna Han Xueyong Zhu Wenli Yu Jenna J. Guthmiller Florian Krammer Patrick C. Wilson Andrew B. Ward Ian A. Wilson |
| author_facet | Ting-Hui Lin Chang-Chun David Lee Monica L. Fernández-Quintero James A. Ferguson Julianna Han Xueyong Zhu Wenli Yu Jenna J. Guthmiller Florian Krammer Patrick C. Wilson Andrew B. Ward Ian A. Wilson |
| author_sort | Ting-Hui Lin |
| collection | DOAJ |
| description | Abstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses. |
| format | Article |
| id | doaj-art-b10af2cead42462c9bcdef13ace26f3d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b10af2cead42462c9bcdef13ace26f3d2025-02-02T12:32:15ZengNature PortfolioNature Communications2041-17232025-02-0116111510.1038/s41467-025-56496-4Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genesTing-Hui Lin0Chang-Chun David Lee1Monica L. Fernández-Quintero2James A. Ferguson3Julianna Han4Xueyong Zhu5Wenli Yu6Jenna J. Guthmiller7Florian Krammer8Patrick C. Wilson9Andrew B. Ward10Ian A. Wilson11Department of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical CampusDepartment of Medicine, Icahn School of Medicine at Mount SinaiDrukier Institute for Children’s Health, Department of Pediatrics, Weill Cornell MedicineDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteAbstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.https://doi.org/10.1038/s41467-025-56496-4 |
| spellingShingle | Ting-Hui Lin Chang-Chun David Lee Monica L. Fernández-Quintero James A. Ferguson Julianna Han Xueyong Zhu Wenli Yu Jenna J. Guthmiller Florian Krammer Patrick C. Wilson Andrew B. Ward Ian A. Wilson Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes Nature Communications |
| title | Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes |
| title_full | Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes |
| title_fullStr | Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes |
| title_full_unstemmed | Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes |
| title_short | Structurally convergent antibodies derived from different vaccine strategies target the influenza virus HA anchor epitope with a subset of VH3 and VK3 genes |
| title_sort | structurally convergent antibodies derived from different vaccine strategies target the influenza virus ha anchor epitope with a subset of vh3 and vk3 genes |
| url | https://doi.org/10.1038/s41467-025-56496-4 |
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