Characterization of Anti-influenza B Hemagglutinin Antibodies 2248890

Abstract

Abstract Introduction Influenza B viruses continue to cause seasonal outbreaks around the world. The mismatch between vaccine and circulating strains was commonly detected in the outbreaks in Taiwan. Co-circulation of both antigenic lineages (Yamagata and Victoria lineages) was frequently found in the outbreaks in Taiwan as well. While antibody immunity plays a major role in the protection against influenza, the information of human antibody response to influenza B virus mainly comes from serological studies. Methods We have detected the induction of antibody-secreting B cell response to influenza B viruses and isolated B cell-derived antibodies from adults status post inactivated influenza vaccination. A panel of human antibodies that react to influenza B hemagglutinin in the binding assays was identified and further characterized in details. Results Each of influenza B antibodies has unique sequence and variable region VDJ rearrangements. Among anti-influenza B hemagglutinin antibodies, a substantial portion showed cross-reactivity with both Yamagata and Victoria lineage hemagglutinins. The majority of lineage-specific and cross-lineage anti-influenza B hemagglutinin antibodies neutralized the corresponding virus in the vaccine. Epitope mapping by selection of escape mutants revealed that neutralizing antibodies recognized the epitopes that surrounds the receptor-binding site. Besides, the influenza B hemagglutinin residue change of circulating strains was tightly related to the loss of neutralization by antibodies, which indicates the occurrence of antigenic change. Conclusion In summary, we dissected the human antibody repertoire against influenza B hemagglutinin induced by vaccination, performed fine epitope mapping of viral hemagglutinin, and demonstrated the role of critical antigenic determinants in the process of antigenic evolution of virus. Funding Source n/a Topic Categories Viral Immunology (VIR)