Site-specific serology unveils cross-reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes
Informazioni aggiuntive
Autori
Paparoditis P. C. G.,
Fruehwirth A.,
Bevc K.,
Low J. S.,
Jerak J.,
Terzaghi L.,
Foglierini M.,
Fernandez B.,
Jarrossay D.,
Corti D.,
Sallusto F.,
Lanzavecchia A.,
Cassotta A.
Tipo
Articolo pubblicato in rivista scientifica
Anno
2024
Lingua
Inglese
Sommario
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.
Parole chiave
Antibodies, Infectious diseases, Vaccination
Periodico
European journal of immunology
Volume
54
Numero ( Mese )
10
Pagine (o numero dell’articolo)
2451045
Diffusione
Licenza
CC BY-NC-ND
Visibilità
Pubblico
Status open access
Hybrid
