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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 684-694.e9 |
| Journal | Cell |
| Volume | 167 |
| Issue number | 3 |
| DOIs | |
| State | Published - Oct 20 2016 |
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Keywords
- antigen specificity
- cross-neutralization
- human monoclonal antibodies
- poxvirus infections
- protective immunity
- smallpox vaccine
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections. / Gilchuk, Iuliia; Gilchuk, Pavlo; Sapparapu, Gopal; Lampley, Rebecca; Singh, Vidisha; Kose, Nurgun; Blum, David L.; Hughes, Laura J.; Satheshkumar, Panayampalli S.; Townsend, Michael B.; Kondas, Ashley V.; Reed, Zachary; Weiner, Zachary; Olson, Victoria A.; Hammarlund, Erika; Raue, Hans Peter; Slifka, Mark; Slaughter, James C.; Graham, Barney S.; Edwards, Kathryn M.; Eisenberg, Roselyn J.; Cohen, Gary H.; Joyce, Sebastian; Crowe, James E.
In: Cell, Vol. 167, No. 3, 20.10.2016, p. 684-694.e9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections
AU - Gilchuk, Iuliia
AU - Gilchuk, Pavlo
AU - Sapparapu, Gopal
AU - Lampley, Rebecca
AU - Singh, Vidisha
AU - Kose, Nurgun
AU - Blum, David L.
AU - Hughes, Laura J.
AU - Satheshkumar, Panayampalli S.
AU - Townsend, Michael B.
AU - Kondas, Ashley V.
AU - Reed, Zachary
AU - Weiner, Zachary
AU - Olson, Victoria A.
AU - Hammarlund, Erika
AU - Raue, Hans Peter
AU - Slifka, Mark
AU - Slaughter, James C.
AU - Graham, Barney S.
AU - Edwards, Kathryn M.
AU - Eisenberg, Roselyn J.
AU - Cohen, Gary H.
AU - Joyce, Sebastian
AU - Crowe, James E.
PY - 2016/10/20
Y1 - 2016/10/20
N2 - 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.
AB - 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.
KW - antigen specificity
KW - cross-neutralization
KW - human monoclonal antibodies
KW - poxvirus infections
KW - protective immunity
KW - smallpox vaccine
UR - http://www.scopus.com/inward/record.url?scp=84992677658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992677658&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2016.09.049
DO - 10.1016/j.cell.2016.09.049
M3 - Article
C2 - 27768891
AN - SCOPUS:84992677658
VL - 167
SP - 684-694.e9
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -