부산대학교 도서관

There is growing appreciation for neuraminidase (NA) as an influenza vaccine target; however, its antigenicity remains poorly characterized. In this study, we isolated three broadly reactive N2 antibodies from the plasmablasts of a single vaccinee, including one that cross-reacts with NAs from seasonal H3N2 strains spanning five decades. Although these three antibodies have diverse germline usages, they recognize similar epitopes that are distant from the NA active site and instead involve the highly conserved underside of NA head domain. We also showed that all three antibodies confer prophylactic and therapeutic protection in vivo , due to both Fc effector functions and NA inhibition through steric hindrance. Additionally, the contribution of Fc effector functions to protection in vivo inversely correlates with viral growth inhibition activity in vitro. Overall, our findings advance the understanding of NA antibody response and provide important insights into the development of a broadly protective influenza vaccine. [Display omitted] • Cryo-EM structures of three clonally distinct NA antibodies (Abs) • NA Abs bind to overlapping conserved epitopes in the underside of NA head domain • Ab epitopes have minimal overlap with other structurally defined NA epitopes • The defined NA Abs inhibit NA activity and confer protection in vivo The immunization potential of antibodies against influenza neuraminidase has been underappreciated. Here, Lei et al. isolated three protective antibodies that cross-react with neuraminidases from seasonal H3N2 strains spanning multiple decades. Structural and functional characterization provides insights into antibody response against influenza neuraminidase with implications for developing broadly protective influenza vaccines. [ABSTRACT FROM AUTHOR]