Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface

• DOI: 10.1016/j.immuni.2024.05.002
• Publication Date: 2024-05-31T14:42:16Z
• Authors: Rachael M. Wolters; James A. Ferguson; Ivette A. Nuñez; Elaine E. Chen; Ty Sornberger; Luke Myers; Svearike Oeverdieck; Sai Sundar Rajan ...; Chandrahaas Kona; Laura S. Handal; Trevor E. Esilu; Edgar Davidson; Benjamin J. Doranz; Taylor B. Engdahl; Nurgun Kose; Lauren E. Williamson; C. Buddy Creech; Katherine N. Gibs...; Andrew B. Ward; James E. Crowe
• Keywords: Virus Replication/drug effects; Orthomyxoviridae Infections/immunology; Human/immunology; Neuraminidase; Antibodies, Monoclonal; Influenza Vaccines/immunology; Antibodies, Viral; Virus Replication; Antibodies; Influenza; Influenza B virus; Mice; Viral Proteins; Orthomyxoviridae Infections; Influenza Vaccines; Influenza, Human; Humans; Animals; Neuraminidase/immunology; Monoclonal/immunology; Viral Proteins/immunology; Influenza B virus/immunology; Viral/immunology

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.