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Cited by 39Influenza Virus Research Studiesvaccines and immunoinformatics approachesMonoclonal and Polyclonal Antibodies Research

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Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection

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Chen, Zhao-Shan, Huang, Hsiang-Chi, Wang, Xiangkun, Schön, Karin, Jia, Yane, Lebens, Michael, Besavilla, Danica F., Murti, Janarthan R., Ji, Yanhong, Sarshad, Aishe A., Deng, Guohua, Zhu, Qiyun, Angeletti, Davide·2025·Nature Communications
DOI 10.1038/s41467-024-55193-yPMC PMC11718266

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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.

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Metadata

Authors
Chen, Z.-S., Huang, H.-C., Wang, X., Schön, K., Jia, Y., Lebens, M., Besavilla, D. F., Murti, J. R., Ji, Y., Sarshad, A. A., Deng, G., Zhu, Q., & Angeletti, D.
Affiliations
  • Lanzhou Veterinary Research Institute (CN)
  • Wallenberg Centre for Molecular and Translational Medicine (SE)
  • University of Gothenburg (SE)
  • Chinese Academy of Agricultural Sciences (CN)
  • Science for Life Laboratory (SE)
Corresponding author
  • Zhu, Qiyun
  • Angeletti, Davide
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-01-09
Volume
16
Issue
1
Pages
432-432
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-55193-y
PMC
PMC11718266
OpenAlex
W4406221636
Cited by
39
References
5
Citations by year
2026: 26 · 2025: 13
FWCI
26.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (32272972, U23A20243, 2021YFD1800204)
  • Svenska Sällskapet för Medicinsk Forskning (S19-0019)
  • Knut och Alice Wallenbergs Stiftelse (850638, 2021.0033, PAR 2020/228)
  • Vetenskapsrådet (2021-01164, 2019-01855, 2021-01165, 850638)
  • Göteborgs Universitet
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
nanobodies, immunodominant epitopes, broadly neutralizing antibodies, heterosubtypic immunity, universal influenza vaccine, peptide immunization, antigenic drift
MeSH terms
Animals, Antibodies, Viral, Cross Reactions, Dogs, Female, Humans, Influenza, Human, Influenza Vaccines, Mice, Inbred BALB C, Orthomyxoviridae Infections, Influenza A virus, Immunodominant Epitopes, Hemagglutinin Glycoproteins, Influenza Virus, Mice, Antibodies, Neutralizing, Single-Domain Antibodies, Madin Darby Canine Kidney Cells

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