@article{9ef734d57c34434da98261a1139c0860,
title = "Cooperativity mediated by rationally selected combinations of human monoclonal antibodies targeting the henipavirus receptor binding protein",
abstract = "Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. The most potent class of cross-reactive antibodies achieves neutralization by blocking viral attachment to the host cell receptors ephrin-B2 and ephrin-B3, with a second class being enhanced by receptor binding. mAbs from both classes display synergistic activity in vitro. In a stringent hamster model of NiV Bangladesh (NiVB) infection, antibodies from both classes reduce morbidity and mortality and achieve synergistic protection in combination. These candidate mAbs might be suitable for use in a cocktail therapeutic approach to achieve synergistic potency and reduce the risk of virus escape.",
keywords = "B lymphocytes, Hendra virus, Nipah virus, antigen-antibody reactions, epitopes, henipavirus infections, monoclonal antibodies, therapy, viral antibodies",
author = "Doyle, {Michael P.} and Nurgun Kose and Viktoriya Borisevich and Elad Binshtein and Moushimi Amaya and Marcus Nagel and Annand, {Edward J.} and Erica Armstrong and Robin Bombardi and Jinhui Dong and Schey, {Kevin L.} and Broder, {Christopher C.} and Larry Zeitlin and Kuang, {Erin A.} and Bornholdt, {Zachary A.} and West, {Brandyn R.} and Geisbert, {Thomas W.} and Cross, {Robert W.} and Crowe, {James E.}",
note = "Funding Information: We thank Chris Gainza and Rachel Nargi from Vanderbilt in the Crowe laboratory for technical support with antibody production and purification; Joseph Reidy, Andrew Trivette, and Robert Carnahan for intellectual contributions to antibody production and sequencing; and Ian Setliff and Ivelin Georgiev for statistical support. We thank Noah Ditto of Carterra for assistance in SPR data analysis. We acknowledge BioRender for use in generating the graphical abstract. This work was supported by a grant from the National Institutes of Health (NIH) U19 AI142764 and departmental funds from UTMB to T.W.G. and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory. The work of M.P.D. was supported by NIH fellowship grant F31 AI152332. The project described was supported by CTSA award no. UL1 TR002243 from the National Center for Advancing Translational Sciences (NCATS). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. Conceptualization, M.P.D. and J.E.C.; methodology, M.P.D. N.K. V.B. K.L.S. E.A.K. and B.R.W.; investigation, M.P.D. N.K. V.B. E.B. M.A. M.N. E.A. R.B. J.D. K.L.S. L.Z. E.A.K. Z.A.B. B.R.W. T.W.G. R.W.C. and J.E.C.; resources, E.J.A. C.C.B. T.W.G. and J.E.C.; writing ? original draft, M.P.D. and J.E.C.; writing ? review & editing, all authors; supervision, C.C.B. T.W.G. and J.E.C.; project administration, T.W.G. and J.E.C.; funding acquisition, M.P.D. L.Z. T.W.G. J.E.C. and C.C.B. J.E.C. has served as a consultant for Luna Biologics, is a member of the Scientific Advisory Board of Meissa Vaccines, and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received unrelated sponsored research agreements from Takeda, IDBiologics, and AstraZeneca. E.A.K. Z.A.B. and B.R.W. are employees and shareholders of Mapp. L.Z. is an employee, shareholder, and co-owner of Mapp. C.C.B. is a US federal employee, and C.C.B. and M.A. are co-inventors on US and foreign patents pertaining to Cedar virus and methods of use and recombinant Cedar virus chimeras, whose assignees are the US as represented by the Henry M. Jackson Foundation for the Advancement of Military Medicine (Bethesda, MD, USA). The remaining authors declare no competing interests. Funding Information: We thank Chris Gainza and Rachel Nargi from Vanderbilt in the Crowe laboratory for technical support with antibody production and purification; Joseph Reidy, Andrew Trivette, and Robert Carnahan for intellectual contributions to antibody production and sequencing; and Ian Setliff and Ivelin Georgiev for statistical support. We thank Noah Ditto of Carterra for assistance in SPR data analysis. We acknowledge BioRender for use in generating the graphical abstract. This work was supported by a grant from the National Institutes of Health (NIH) U19 AI142764 and departmental funds from UTMB to T.W.G. and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory. The work of M.P.D. was supported by NIH fellowship grant F31 AI152332 . The project described was supported by CTSA award no. UL1 TR002243 from the National Center for Advancing Translational Sciences (NCATS). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAID or NIH. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = aug,
day = "31",
doi = "10.1016/j.celrep.2021.109628",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}