Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

Taylor B. Engdahl; Natalia A. Kuzmina; Adam Ronk; Chad Mire; Matthew A. Hyde; Nurgun Kose; Matthew D. Josleyn; Rachel E. Sutton; Apoorva Mehta; Rachael M. Wolters; Nicole M. Lloyd; Francisca R. Valdivieso; Thomas G. Ksiazek; Jay W. Hooper; Alexander Bukreyev; James E. Crowe

doi:10.1016/j.celrep.2021.109086

Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

Taylor B. Engdahl, Natalia A. Kuzmina, Adam Ronk, Chad Mire, Matthew A. Hyde, Nurgun Kose, Matthew D. Josleyn, Rachel E. Sutton, Apoorva Mehta, Rachael M. Wolters, Nicole M. Lloyd, Francisca R. Valdivieso, Thomas G. Ksiazek, Jay W. Hooper, Alexander Bukreyev, James E. Crowe

Pathology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	109086
Journal	Cell Reports
Volume	35
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2021.109086
State	Published - May 4 2021

Keywords

Andes virus
Bunyavirus
Sin Nombre virus
antibody
cross-reactivity
hantavirus
infection

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2021.109086

Cite this

Engdahl, T. B., Kuzmina, N. A., Ronk, A., Mire, C., Hyde, M. A., Kose, N., Josleyn, M. D., Sutton, R. E., Mehta, A., Wolters, R. M., Lloyd, N. M., Valdivieso, F. R., Ksiazek, T. G., Hooper, J. W., Bukreyev, A., & Crowe, J. E. (2021). Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection. Cell Reports, 35(5), Article 109086. https://doi.org/10.1016/j.celrep.2021.109086

Engdahl, TB, Kuzmina, NA, Ronk, A, Mire, C, Hyde, MA, Kose, N, Josleyn, MD, Sutton, RE, Mehta, A, Wolters, RM, Lloyd, NM, Valdivieso, FR, Ksiazek, TG, Hooper, JW, Bukreyev, A & Crowe, JE 2021, 'Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection', Cell Reports, vol. 35, no. 5, 109086. https://doi.org/10.1016/j.celrep.2021.109086

@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 Adam Ronk and Chad Mire 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 = "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",

}

TY - JOUR

T1 - Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

AU - Engdahl, Taylor B.

AU - Kuzmina, Natalia A.

AU - Ronk, Adam

AU - Mire, Chad

AU - Hyde, Matthew A.

AU - Kose, Nurgun

AU - Josleyn, Matthew D.

AU - Sutton, Rachel E.

AU - Mehta, Apoorva

AU - Wolters, Rachael M.

AU - Lloyd, Nicole M.

AU - Valdivieso, Francisca R.

AU - Ksiazek, Thomas G.

AU - Hooper, Jay W.

AU - Bukreyev, Alexander

AU - Crowe, James E.

PY - 2021/5/4

Y1 - 2021/5/4

N2 - 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.

AB - 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.

KW - Andes virus

KW - Bunyavirus

KW - Sin Nombre virus

KW - antibody

KW - cross-reactivity

KW - hantavirus

KW - infection

UR - http://www.scopus.com/inward/record.url?scp=85105077638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85105077638&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2021.109086

DO - 10.1016/j.celrep.2021.109086

M3 - Article

C2 - 33951434

AN - SCOPUS:85105077638

SN - 2211-1247

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 109086

ER -

Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this