@article{0c3616fc6b4d4276af482c91435ba73a,
title = "Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein",
abstract = "Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.",
keywords = "B lymphocytes, Hendra virus, Henipavirus infections, Nipah virus, antibodies, antigen-antibody reactions, epitopes, molecular structure, monoclonal, pre-exposure prophylaxis, receptor binding protein, therapy, viral",
author = "Jinhui Dong and Cross, {Robert W.} and Doyle, {Michael P.} and Nurgun Kose and Mousa, {Jarrod J.} and Annand, {Edward J.} and Viktoriya Borisevich and Agans, {Krystle N.} and Rachel Sutton and Rachel Nargi and Mahsa Majedi and Fenton, {Karla A.} and Walter Reichard and Bombardi, {Robin G.} and Geisbert, {Thomas W.} and Crowe, {James E.}",
note = "Funding Information: We thank Rachel Nargi from Vanderbilt in the Crowe laboratory for technical support with antibody production and purification, Robert Carnahan for intellectual contributions to antibody production and sequencing, and Christopher Broder for helpful scientific conversations. We also thank Mathew Hyde and the UTMB Animal Resource Center for their assistance with animal procedures. This work was supported by a grant from the National Institutes of Health (NIH) U19 AI142764 and departmental funds from UTMB to Thomas Geisbert. 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. X-ray diffraction data were collected at Beamline 21-ID-G at the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (grant 085P1000817). Support for crystallography was provided from the Vanderbilt Center for Structural Biology. The graphical abstract was made in part with BioRender.com. Conceptualization, J.E.C.; Methodology, J.D. R.W.C. M.P.D. N.K. and R.G.B.; Investigation, J.D. R.W.C. M.P.D. N.K. J.J.M. R.G.B. V.B. K.N.A. M.M. K.A.F. W.R. and T.W.G.; Resources, E.J.A. and T.W.G. and J.E.C.; Writing ? Original Draft, J.D. J.E.C. and M.P.D.; Writing ? Review & Editing, all authors; Supervision, T.W.G. and J.E.C.; Project Administration, T.W.G. and J.E.C.; Funding Acquisition, T.W.G. and J.E.C. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax; is on the Scientific Advisory Boards of CompuVax, GigaGen, Meissa Vaccines; and is founder of IDBiologics, Inc. Vanderbilt University has applied for a patent related to antibodies described in this paper. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = dec,
day = "10",
doi = "10.1016/j.cell.2020.11.023",
language = "English (US)",
volume = "183",
pages = "1536--1550.e17",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "6",
}