1. Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface.
- Author
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Wolters RM, Ferguson JA, Nuñez IA, Chen EE, Sornberger T, Myers L, Oeverdieck S, Raghavan SSR, Kona C, Handal LS, Esilu TE, Davidson E, Doranz BJ, Engdahl TB, Kose N, Williamson LE, Creech CB, Gibson-Corley KN, Ward AB, and Crowe JE Jr
- Subjects
- Humans, Animals, Influenza Vaccines immunology, Mice, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections prevention & control, Viral Proteins immunology, Virus Replication drug effects, Neuraminidase immunology, Influenza B virus immunology, Antibodies, Monoclonal immunology, Antibodies, Viral immunology, Influenza, Human immunology, Influenza, Human prevention & control
- 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., Competing Interests: Declaration of interests L.E.W. serves as a consultant for BigHat Biosciences. The content of this article is solely the responsibility of the authors and does not represent the official views of BigHat Biosciences. C.B.C. serves as a consultant to GlaxoSmithKline, Sanofi, TDCowen Investments, Guidepoint Global, Debiopharm, and CommenseBio and receives royalties from UpToDate. The laboratory of C.B.C. receives funding for unrelated work from Moderna. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, GlaxoSmithKline, and BTG International Inc; is a member of the Scientific Advisory Board of Meissa Vaccines; a former member of the Scientific Advisory Board of Gigagen (Grifols); and is founder of IDBiologics. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda, and IDBiologics during the conduct of the study. The opinions, interpretations, conclusions, and recommendations contained herein are those of the authors and are not necessarily endorsed by the US Department of Defense. E.D., T.E.E., and B.J.D. are employees of Integral Molecular, B.J.D. is a shareholder of Integral Molecular. Vanderbilt University has applied for a patent pertinent to some of the materials in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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