8EZ8

Structure of 3C08 Fab in complex with A/Moscow/10/1999 (H3N2) influenza virus neuraminidase

Summary for 8EZ8

• Entry DOI: 10.2210/pdb8ez8/pdb
• EMDB information: 28730
• Descriptor: Heavy chain of influenza virus neuraminidase antibody 3C08, Light chain of influenza virus neuraminidase antibody 3C08, Neuraminidase, ... (6 entities in total)
• Functional Keywords: antibody, neuraminidase, influenza, hydrolase-immune system complex, hydrolase/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 69406.59

Authors

Mou, Z.,Lei, R.,Wu, N.C.,Dai, X. (deposition date: 2022-10-31, release date: 2023-11-08, Last modification date: 2024-11-06)

Primary citation

Lei, R.,Kim, W.,Lv, H.,Mou, Z.,Scherm, M.J.,Schmitz, A.J.,Turner, J.S.,Tan, T.J.C.,Wang, Y.,Ouyang, W.O.,Liang, W.,Rivera-Cardona, J.,Teo, C.,Graham, C.S.,Brooke, C.B.,Presti, R.M.,Mok, C.K.P.,Krammer, F.,Dai, X.,Ellebedy, A.H.,Wu, N.C.
Leveraging vaccination-induced protective antibodies to define conserved epitopes on influenza N2 neuraminidase.
Immunity, 56:2621-, 2023

PubMed 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.

PubMed: 37967533
DOI: 10.1016/j.immuni.2023.10.005

Experimental method

ELECTRON MICROSCOPY (2.78 Å)