8U1S

A mechanistic understanding of protective influenza B neuraminidase mAbs at the airway interface

Summary for 8U1S

• Entry DOI: 10.2210/pdb8u1s/pdb
• EMDB information: 41826
• Descriptor: Neuraminidase, mAb-393 heavy chain, mAb-393 light chain, ... (4 entities in total)
• Functional Keywords: neuraminidase sialidase, hydrolase
• Biological source: Influenza B virus (B/Iowa/06/2017); More
• Total number of polymer chains: 12
• Total formula weight: 307151.09

Authors

Ferguson, J.A.,Raghavan, S.S.R.,Ward, A.B. (deposition date: 2023-09-02, release date: 2024-03-27, Last modification date: 2025-04-09)

Primary citation

Wolters, R.M.,Ferguson, J.A.,Nunez, I.A.,Chen, E.E.,Sornberger, T.,Myers, L.,Oeverdieck, S.,Raghavan, S.S.R.,Kona, C.,Handal, L.S.,Esilu, T.E.,Davidson, E.,Doranz, B.J.,Engdahl, T.B.,Kose, N.,Williamson, L.E.,Creech, C.B.,Gibson-Corley, K.N.,Ward, A.B.,Crowe Jr., J.E.
Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface.
Immunity, 57:1413-1427.e9, 2024

PubMed Abstract: Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically in vivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication in vitro in primary human respiratory epithelial cell cultures and protected against IBV in vivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates.

PubMed: 38823390
DOI: 10.1016/j.immuni.2024.05.002

Experimental method

ELECTRON MICROSCOPY (3.21 Å)