Breadth of antibody activity elicited by an influenza B hemagglutinin vaccine is influenced by pre-existing immune responses to influenza B viruses.

UNLABELLED: Most people are exposed to influenza A and influenza B viruses (IBV) at an early age through natural infection or vaccination. These previous exposures can shape future immune responses and the ability to either recall memory B cells or generate de novo immune responses. Therefore, it is important to consider pre-existing immunity when testing vaccine candidates. The B/Victoria (B/VIC) and the B/Yamagata (B/YAM) lineages circulated in the human population between 1987 and 2020 until the B/YAM lineage stopped circulating following the coronavirus disease 2019 pandemic. Most people born prior to 2020 have pre-existing immune responses to both lineages of IBV. Therefore, in this report, the impact of vaccine-induced antibodies was explored in mice with pre-existing immune responses to B/YAM or B/VIC viruses alone or in combination. The recalled B cell responses induced by modern wild-type hemagglutinin (HA) vaccines from each IBV lineage were compared to the recalled B cell responses elicited by a broadly reactive antigen, B-COBRA-2 (BC2) HA, which elicits cross-lineage neutralizing antibodies. This report highlights the lineage specificity of immunological imprinting with IBV and demonstrates the antigen-specific activation of antibody-secreting B cells by broadly reactive antigens.

IMPORTANCE: This report demonstrates how varying immunological backgrounds to influenza B virus influence vaccine-induced responses in mice. It further highlights that a broadly reactive influenza B virus hemagglutinin (HA) antigen stimulates higher levels of IgM-secreting cells compared to wild-type HA antigens.