Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase

Ruipeng Lei, Wooseob Kim, Huibin Lv, Zongjun Mou, Michael J. Scherm, Aaron J. Schmitz, Jackson S. Turner, Timothy J.C. Tan, Yiquan Wang, Wenhao O. Ouyang, Weiwen Liang, Joel Rivera-Cardona, Chuyun Teo, Claire S. Graham, Christopher B. Brooke, Rachel M. Presti, Chris K.P. Mok, Florian Krammer, Xinghong Dai, Ali H. EllebedyNicholas C. Wu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2621-2634.e6
Issue number11
StatePublished - Nov 14 2023


  • antibody
  • cross-reactive
  • cryo-EM
  • influenza virus
  • neuraminidase
  • protective
  • structures
  • vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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