Interrogating human B cell immunity to inform universal influenza vaccine design

Wheatley AK

Department of Microbiology and Immunology, University of Melbourne.

Influenza inflicts significant global mortality and morbidity that can be combated by effective immunisation. However, the protective efficacy of current vaccines is limited by the variability and rapid mutagenesis of circulating strains. There is tremendous interest in developing universal influenza vaccines for life-long protection. Here, we use recombinant analogues of the viral hemagglutinin protein and flow cytometry to interrogate human B cell and antibody responses to influenza. Our approach enables the enumeration and phenotypic characterisation of B cell responses to seasonal influenza vaccines. In addition, we can pan the B cell repertoire for rare specificities allowing near universal influenza recognition and in some cases protection. Theses approaches allow the identification of potentially protective epitopes and may inform the design of next-generation influenza vaccines. In addition, we can recover human monoclonal antibodies with potential prophylactic, therapeutic, or diagnostic applications for eventual clinical use.