@article{f9ffb1978c6946a5904914572c341b90,
title = "Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections",
abstract = "Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.",
keywords = "antigen specificity, cross-neutralization, human monoclonal antibodies, poxvirus infections, protective immunity, smallpox vaccine",
author = "Iuliia Gilchuk and Pavlo Gilchuk and Gopal Sapparapu and Rebecca Lampley and Vidisha Singh and Nurgun Kose and Blum, {David L.} and Hughes, {Laura J.} and Satheshkumar, {Panayampalli S.} and Townsend, {Michael B.} and Kondas, {Ashley V.} and Zachary Reed and Zachary Weiner and Olson, {Victoria A.} and Erika Hammarlund and Raue, {Hans Peter} and Slifka, {Mark K.} and Slaughter, {James C.} and Graham, {Barney S.} and Edwards, {Kathryn M.} and Eisenberg, {Roselyn J.} and Cohen, {Gary H.} and Sebastian Joyce and Crowe, {James E.}",
note = "Funding Information: This project received support from the U.S. NIH (grants U01 AI48512 and contract HHSN272200900047C to J.E.C., and U19 AI109948 and 8P51 OD 011092-53 to M.K.S.). The project was supported by NCRR grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06, and VA Merit Award BX001444 (to S.J.). This work was supported by intramural funding from the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH. Flow cytometry experiments were performed in the Vanderbilt University Medical Center Flow Cytometry Shared Resource, supported by NIH P30 CA68485 and DK058404. We thank Jill Janssen and the Vanderbilt Clinical Trials Center for regulatory support, and Yingchun Yu, Patricia McGraw, Natalie Thornburg, Shane Crotty, Chwan Hong Foo, J. Charles Whitbeck, and Stuart Isaacs for technical contributions and advice. We thank Y. Xiang and Dirk Zajonc for providing recombinant D8 protein and Shane Crotty for providing H3 protein. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Centers for Disease Control and Prevention. I.G. and J.E.C. are named as co-inventors on a patent applied for that is associated with some of the antibodies described in this manuscript. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = oct,
day = "20",
doi = "10.1016/j.cell.2016.09.049",
language = "English (US)",
volume = "167",
pages = "684--694.e9",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}