@article{6e0fe80e10834377a90c7053190768c7,
title = "Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection",
abstract = "New World hantaviruses (NWHs) are endemic in North and South America and cause hantavirus cardiopulmonary syndrome (HCPS), with a case fatality rate of up to 40%. Knowledge of the natural humoral immune response to NWH infection is limited. Here, we describe human monoclonal antibodies (mAbs) isolated from individuals previously infected with Sin Nombre virus (SNV) or Andes virus (ANDV). Most SNV-reactive antibodies show broad recognition and cross-neutralization of both New and Old World hantaviruses, while many ANDV-reactive antibodies show activity for ANDV only. mAbs ANDV-44 and SNV-53 compete for binding to a distinct site on the ANDV surface glycoprotein and show potently neutralizing activity to New and Old World hantaviruses. Four mAbs show therapeutic efficacy at clinically relevant doses in hamsters. These studies reveal a convergent and potently neutralizing human antibody response to NWHs and suggest therapeutic potential for human mAbs against HCPS.",
keywords = "Andes virus, Bunyavirus, Sin Nombre virus, antibody, cross-reactivity, hantavirus, infection",
author = "Engdahl, {Taylor B.} and Kuzmina, {Natalia A.} and Ronk, {Adam J.} and Mire, {Chad E.} and Hyde, {Matthew A.} and Nurgun Kose and Josleyn, {Matthew D.} and Sutton, {Rachel E.} and Apoorva Mehta and Wolters, {Rachael M.} and Lloyd, {Nicole M.} and Valdivieso, {Francisca R.} and Ksiazek, {Thomas G.} and Hooper, {Jay W.} and Alexander Bukreyev and Crowe, {James E.}",
note = "Funding Information: At Vanderbilt, we thank R. Carnahan, P. Gilchuk, S. Zost, and C. Slaughter for intellectual contributions and training and R. Irving and R. Nargi for managerial support. We thank E. Armstrong, J. Rodriguez, C. Gainza, J. Reidy, A. Trivette, and R. Troseth for technical support. We thank M. Leksell, M. Mayo, K. Moton, T. Martin, G. DeBellis, A. Bunnell, and A. Jordan for administrative assistance. We acknowledge the UTMB Animal Resource Center for the animal study{\textquoteright}s support and thank M. Milazzo at UTMB for facilitating BSL-3 and ABSL-4 training and transferring viral isolates. We acknowledge C. Spiropoulou at the CDC for providing rabbit anti-SNV polyclonal sera. In Chile, we acknowledge A. Cuiza for enrolling the ANDV patients and obtaining the ANDV samples and C. Vial for preparing the PBMCs from ANDV patients. The work of T.B.E. was supported by the NIH (training grant 5T32GM008320-30 ). This project received support from the Military Infectious Disease Research Program, Program Area T (project MI210048 ). The graphical abstract was made in part with BioRender.com . Funding Information: At Vanderbilt, we thank R. Carnahan, P. Gilchuk, S. Zost, and C. Slaughter for intellectual contributions and training and R. Irving and R. Nargi for managerial support. We thank E. Armstrong, J. Rodriguez, C. Gainza, J. Reidy, A. Trivette, and R. Troseth for technical support. We thank M. Leksell, M. Mayo, K. Moton, T. Martin, G. DeBellis, A. Bunnell, and A. Jordan for administrative assistance. We acknowledge the UTMB Animal Resource Center for the animal study's support and thank M. Milazzo at UTMB for facilitating BSL-3 and ABSL-4 training and transferring viral isolates. We acknowledge C. Spiropoulou at the CDC for providing rabbit anti-SNV polyclonal sera. In Chile, we acknowledge A. Cuiza for enrolling the ANDV patients and obtaining the ANDV samples and C. Vial for preparing the PBMCs from ANDV patients. The work of T.B.E. was supported by the NIH (training grant 5T32GM008320-30). This project received support from the Military Infectious Disease Research Program, Program Area T (project MI210048). The graphical abstract was made in part with BioRender.com. Conceptualization, T.B.E. A.B. and J.E.C.; methodology, T.B.E. A.B. J.W.H. and J.E.C.; investigation, T.B.E. N.A.K. A.J.R. C.E.M. M.A.H. N.K. M.D.J. R.E.S. A.M. R.M.W. and N.M.L.; writing ? original draft, T.B.E. and J.E.C.; writing ? review & editing, T.B.E. A.B. N.A.K. J.W.H. and J.E.C. (all authors edited and approved the final version); funding acquisition, A.B. J.W.H. and J.E.C.; resources, F.R.V.; supervision, A.B. T.G.K. J.W.H. and J.E.C. J.E.C. has served as a consultant for Eli Lilly, GlaxoSmithKline, and Luna Biologics; is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines; and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received unrelated sponsored research agreements from Takeda Vaccines, IDBiologics, and AstraZeneca. Vanderbilt University has applied for patents concerning hantavirus antibodies that are related to this work. All of the other authors declare no competing interests. Opinions, interpretations, conclusions, and recommendations contained herein are those of the authors and are not necessarily endorsed by the US Department of Defense. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = may,
day = "4",
doi = "10.1016/j.celrep.2021.109086",
language = "English (US)",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}