@article{e4bbc7fe2a164b1d9d09d108a8eb8095,
title = "Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective",
abstract = "Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). Neuraminidase (NA), the second major surface protein on the influenza virus, is emerging as a target of broadly protective antibodies that recognize the NA active site of IAVs. However, similarly broadly protective antibodies against IBV NA have not been identified. Here, we isolated and characterized human monoclonal antibodies (mAbs) that target IBV NA from an IBV-infected patient. Two mAbs displayed broad and potent capacity to inhibit IBV NA enzymatic activity, neutralize the virus in vitro, and protect against lethal IBV infection in mice in prophylactic and therapeutic settings. These mAbs inserted long CDR-H3 loops into the NA active site, engaging residues highly conserved among IBV NAs. These mAbs provide a blueprint for the development of improved vaccines and therapeutics against IBVs.",
keywords = "B cells, Human, Infection, Influenza B virus, Monoclonal antibodies, Neuraminidase, Plasmablasts",
author = "Anders Madsen and Dai, {Ya Nan} and Meagan McMahon and Schmitz, {Aaron J.} and Turner, {Jackson S.} and Jessica Tan and Tingting Lei and Alsoussi, {Wafaa B.} and Shirin Strohmeier and Mostafa Amor and Mohammed, {Bassem M.} and Mudd, {Philip A.} and Viviana Simon and Cox, {Rebecca J.} and Fremont, {Daved H.} and Florian Krammer and Ellebedy, {Ali H.}",
note = "Funding Information: We would like to thank S. House and the clinical sample collection team in the Washington University Emergency Care and Research Core. We thank J. Fitzpatrick and M. Rau of the Washington University Center for Cellular Imaging for assistance with cryo-EM data collection. The EDFLU study was reviewed and approved by the Washington University Institutional Review Board (approval no. 2017-10-220). Work in the Ellebedy laboratory was supported by NIAID R21 AI139813, U01 AI141990, and NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400006C ). The Krammer laboratory was supported by NIAID (grant R01 AI117287 ), NIAID CEIRS (contract HHSN272201400008C ), and NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC, contract 75N93019C00051 ). Work in the Fremont lab was supported by NIAID (CSGID, contract HHSN272201700060C ). The Influenza Centre is funded by the Ministry of Health and Care Services , Norway, the Norwegian Research Council Globvac ( 284930 ), National Graduate School in Infection Biology and Antimicrobials (IBA, 249062 ), the European Union ( EU IMI115672 , FLUCOP), EU Nanomedicines Flunanoair (ERA-NETet EuroNanoMed2, JTC2016 ), and the K.G. Jebsen Centre for Influenza Vaccine Research . Human sample collection was supported by a grant from the Washington University Institute of Clinical and Translational Sciences to P.A.M., which is, in part, supported by the NIH/National Center for Advancing Translational Sciences (NCATS, CTSA grant UL1TR002345 ). A.M. received funding for this work from the Norway-America Association (NORAM) and the National Graduate School in Infection Biology and Antimicrobials (IBA). J.S.T. was supported by NIAID 5T32CA009547 . The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The manuscript was edited by the Scientific Editing Service of the Institute of Clinical and Translational Sciences at Washington University, which is supported by an NIH Clinical and Translational Science Award ( UL1 TR002345 ). Funding Information: We would like to thank S. House and the clinical sample collection team in the Washington University Emergency Care and Research Core. We thank J. Fitzpatrick and M. Rau of the Washington University Center for Cellular Imaging for assistance with cryo-EM data collection. The EDFLU study was reviewed and approved by the Washington University Institutional Review Board (approval no. 2017-10-220). Work in the Ellebedy laboratory was supported by NIAID R21 AI139813, U01 AI141990, and NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400006C). The Krammer laboratory was supported by NIAID (grant R01 AI117287), NIAID CEIRS (contract HHSN272201400008C), and NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC, contract 75N93019C00051). Work in the Fremont lab was supported by NIAID (CSGID, contract HHSN272201700060C). The Influenza Centre is funded by the Ministry of Health and Care Services, Norway, the Norwegian Research Council Globvac (284930), National Graduate School in Infection Biology and Antimicrobials (IBA, 249062), the European Union (EU IMI115672, FLUCOP), EU Nanomedicines Flunanoair (ERA-NETet EuroNanoMed2, JTC2016), and the K.G. Jebsen Centre for Influenza Vaccine Research. Human sample collection was supported by a grant from the Washington University Institute of Clinical and Translational Sciences to P.A.M. which is, in part, supported by the NIH/National Center for Advancing Translational Sciences (NCATS, CTSA grant UL1TR002345). A.M. received funding for this work from the Norway-America Association (NORAM) and the National Graduate School in Infection Biology and Antimicrobials (IBA). J.S.T. was supported by NIAID 5T32CA009547. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. The manuscript was edited by the Scientific Editing Service of the Institute of Clinical and Translational Sciences at Washington University, which is supported by an NIH Clinical and Translational Science Award (UL1 TR002345). A.M. Y.-N.D. M.M. A.J.S. J.T. T.L. W.A.B. S.S. M.A. B.M.M. and V.S. characterized the antibodies; A.J.S. J.S.T. and P.A.M. isolated the antibodies; and A.M. Y.-N.D. R.J.C. D.H.F. F.K. and A.H.E. conceptualized the study and wrote the manuscript. A.H.E. is a consultant for Inbios and Fimbrion Therapeutics. D.H.F. is a co-founder of Courier Therapeutics. The Ellebedy and Fremont laboratories received funding under a sponsored research agreement from Emergent BioSolutions for work that is not related to the data presented in this manuscript. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "13",
doi = "10.1016/j.immuni.2020.08.015",
language = "English",
volume = "53",
pages = "852--863.e7",
journal = "Immunity",
issn = "1074-7613",
number = "4",
}