Site-specific serology unveils cross-reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes
Additional information
Authors
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.
Type
Journal Article
Year
2024
Language
English
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.
Keywords
Antibodies, Infectious diseases, Vaccination
Journal
European journal of immunology
Volume
54
Number ( Month )
10
Pages (or article number)
2451045
Diffusion
License
CC BY-NC-ND
Visibility
Public
Status open access
Hybrid
