GC B Cells, Tfh Cells, and Influenza bnAbs : Insights for Improving Universal Vaccine Design

Antibodies are crucial for providing protection against influenza virus infection; however, protective humoral immunity is limited by antigenic drift and shift. Hence, the discovery of broadly neutralizing antibodies (bnAbs) targeting conserved epitopes on hemagglutinin protein evokes the hope of developing a universal influenza vaccine. Because of such historical reasons, much of the effort in universal vaccine design has focused on B cell epitopes. In contrast, despite the critical role of T follicular helper cells in bnAb induction, T cell epitopes have received far less attention. In this review, we summarize the cellular and molecular factors that impact the bnAb development and discuss key limitation factors that restrict their efficient induction.