A comparative study of H5N1-specific memory B cell repertoires and antibody responses in diverse populations 4259

Abstract Description The highly pathogenic avian influenza A (H5N1) virus remains a major public health threat due to its potential to cause pandemics. Broadly neutralizing antibodies could be key to developing effective treatments and vaccines. This study investigates and compares the memory B cell responses to H5N1 in populations from the United States and South Africa to identify suitable epitopes for broadly neutralizing antibodies with broad efficacy that can fight different strains of the virus. Using advanced techniques like single-cell sequencing and antigen-specific sorting, we analyzed the diversity of memory B cells, focusing on immunoglobulin gene usage, clonal expansion and somatic hypermutation rates, and epitope targeting diversity. Our findings reveal both shared and unique patterns in the B cell responses of these populations, shaped by genetic factors and prior exposure to the virus or vaccines. We identified several high-affinity antibodies that are highly effective and cross-reactive against other influenza strains, with structural studies pinpointing conserved viral epitopes as critical targets. These differences and similarities in immune responses emphasize the importance of considering diverse populations when developing universal vaccines. This research advances our understanding of the immune system’s ability to fight H5N1 and emphasizes the need for global collaboration in developing solutions for emerging infectious diseases. Topic Categories Vaccines and Immunotherapy (VAC)