Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Iuliia Gilchuk; Pavlo Gilchuk; Gopal Sapparapu; Rebecca Lampley; Vidisha Singh; Nurgun Kose; David L. Blum; Laura J. Hughes; Panayampalli S. Satheshkumar; Michael B. Townsend; Ashley V. Kondas; Zachary Reed; Zachary Weiner; Victoria A. Olson; Erika Hammarlund; Hans Peter Raue; Mark K. Slifka; James C. Slaughter; Barney S. Graham; Kathryn M. Edwards; Roselyn J. Eisenberg; Gary H. Cohen; Sebastian Joyce; James E. Crowe

doi:10.1016/j.cell.2016.09.049

Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Iuliia Gilchuk, Pavlo Gilchuk, Gopal Sapparapu, Rebecca Lampley, Vidisha Singh, Nurgun Kose, David L. Blum, Laura J. Hughes, Panayampalli S. Satheshkumar, Michael B. Townsend, Ashley V. Kondas, Zachary Reed, Zachary Weiner, Victoria A. Olson, Erika Hammarlund, Hans Peter Raue, Mark K. Slifka, James C. Slaughter, Barney S. Graham, Kathryn M. EdwardsRoselyn J. Eisenberg, Gary H. Cohen, Sebastian Joyce, James E. Crowe

Oregon National Primate Research Center

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

119 Scopus citations

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	https://doi.org/10.1016/j.cell.2016.09.049
State	Published - Oct 20 2016

Keywords

antigen specificity
cross-neutralization
human monoclonal antibodies
poxvirus infections
protective immunity
smallpox vaccine

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2016.09.049

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Gilchuk, I., Gilchuk, P., Sapparapu, G., Lampley, R., Singh, V., Kose, N., Blum, D. L., Hughes, L. J., Satheshkumar, P. S., Townsend, M. B., Kondas, A. V., Reed, Z., Weiner, Z., Olson, V. A., Hammarlund, E., Raue, H. P., Slifka, M. K., Slaughter, J. C., Graham, B. S., ... Crowe, J. E. (2016). Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections. Cell, 167(3), 684-694.e9. https://doi.org/10.1016/j.cell.2016.09.049

Gilchuk, I, Gilchuk, P, Sapparapu, G, Lampley, R, Singh, V, Kose, N, Blum, DL, Hughes, LJ, Satheshkumar, PS, Townsend, MB, Kondas, AV, Reed, Z, Weiner, Z, Olson, VA, Hammarlund, E, Raue, HP, Slifka, MK, Slaughter, JC, Graham, BS, Edwards, KM, Eisenberg, RJ, Cohen, GH, Joyce, S & Crowe, JE 2016, 'Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections', Cell, vol. 167, no. 3, pp. 684-694.e9. https://doi.org/10.1016/j.cell.2016.09.049

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AU - Sapparapu, Gopal

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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 K.

AU - Slaughter, James C.

AU - Graham, Barney S.

AU - Edwards, Kathryn M.

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AU - Cohen, Gary H.

AU - Joyce, Sebastian

AU - Crowe, James E.

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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.

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KW - protective immunity

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Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Abstract

Keywords

ASJC Scopus subject areas

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