@article{aec36e2530e847349015b079e755dfa3,
title = "Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase",
abstract = "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.",
keywords = "antibody, cross-reactive, cryo-EM, influenza virus, neuraminidase, protective, structures, vaccination",
author = "Ruipeng Lei and Wooseob Kim and Huibin Lv and Zongjun Mou and Scherm, {Michael J.} and Schmitz, {Aaron J.} and Turner, {Jackson S.} and Tan, {Timothy J.C.} and Yiquan Wang and Ouyang, {Wenhao O.} and Weiwen Liang and Joel Rivera-Cardona and Chuyun Teo and Graham, {Claire S.} and Brooke, {Christopher B.} and Presti, {Rachel M.} and Mok, {Chris K.P.} and Florian Krammer and Xinghong Dai and Ellebedy, {Ali H.} and Wu, {Nicholas C.}",
note = "We are grateful to the cryo-EM Core and the Core Facility for Advanced Research Computing at Case Western Reserve University for access of cryo-EM instrumentation and data-processing resources, respectively. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education 2021R1A6A3A03041509 (W.K.), the Calmette and Yersin scholarship from the Pasteur International Network Association (H.L.), the Emergency Key Program of Guangzhou Laboratory (grant no. EKPG22-30-6 ) (C.K.P.M.), the visiting scientist scheme from Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore (C.K.P.M.) , National Institutes of Health (NIH) R01 AI165475 (N.C.W.), DP2 AT011966 (N.C.W.), U01 AI141990 (A.H.E.), U01 AI150747 (A.H.E.), U01 AI144616 (A.H.E.), the Michelson Prizes for Human Immunology and Vaccine Research (N.C.W.), and the Searle Scholars Program (N.C.W.). This study was also partially supported by the NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00014 (F.K.) and by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00051 (F.K.).",
year = "2023",
month = nov,
day = "14",
doi = "10.1016/j.immuni.2023.10.005",
language = "English (US)",
volume = "56",
pages = "2621--2634.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "11",
}