Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes

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Abstract: Efficient identification of human monoclonal antibodies targeting specific antigenic sites is pivotal for advancing vaccines and immunotherapies against infectious diseases and cancer. Existing screening techniques, however, limit our ability to discover monoclonal antibodies with desired specificity. In this study, we introduce a novel method, blocking of binding (BoB) enzyme‐linked immunoassay (ELISA), enabling the detection of high‐avidity human antibodies directed to defined epitopes. Leveraging BoB‐ELISA, we analyzed the antibody response to known epitopes of influenza A hemagglutinin (HA) in the serum of vaccinated donors. Our findings revealed that serum antibodies targeting head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent. Extending our analysis across multiple HA strains, we examined the cross‐reactive antibody response targeting the stem epitope. Importantly, employing BoB‐ELISA we identified donors harboring potent heterosubtypic antibodies targeting the HA stem. B‐cell clonal analysis of these donors revealed three novel, genealogically independent monoclonal antibodies with broad cross‐reactivity to multiple HAs. In summary, we demonstrated that BoB‐ELISA is a sensitive technique for measuring B‐cell epitope immunogenicity, enabling the identification of novel monoclonal antibodies with implications for enhanced vaccine development and immunotherapies.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes ; day:19 ; month:07 ; year:2024 ; extent:17
European journal of immunology ; (19.07.2024) (gesamt 17)

Creator: Paparoditis, Philipp
Fruehwirth, Alexander
Bevc, Kajetana
Low, Jun Siong
Jerak, Josipa
Terzaghi, Laura
Foglierini, Mathilde
Fernandez, Blanca
Jarrossay, David
Corti, Davide
Sallusto, Federica
Lanzavecchia, Antonio
Cassotta, Antonino

DOI: 10.1002/eji.202451045

URN: urn:nbn:de:101:1-2407201408005.811839250204

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 11:01 AM CEST

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Associated

Paparoditis, Philipp
Fruehwirth, Alexander
Bevc, Kajetana
Low, Jun Siong
Jerak, Josipa
Terzaghi, Laura
Foglierini, Mathilde
Fernandez, Blanca
Jarrossay, David
Corti, Davide
Sallusto, Federica
Lanzavecchia, Antonio
Cassotta, Antonino

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Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes

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Other Objects (12)

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