Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement

Philipp A. Ilinykh; Kai Huang; Bronwyn M. Gunn; Natalia A. Kuzmina; Kritika Kedarinath; Eduardo Jurado-Cobena; Fuchun Zhou; Chandru Subramani; Matthew A. Hyde; Jalene V. Velazquez; Lauren E. Williamson; Pavlo Gilchuk; Robert H. Carnahan; Galit Alter; James E. Crowe; Alexander Bukreyev

doi:10.1038/s42003-024-06556-0

Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement

Philipp A. Ilinykh, Kai Huang, Bronwyn M. Gunn, Natalia A. Kuzmina, Kritika Kedarinath, Eduardo Jurado-Cobena, Fuchun Zhou, Chandru Subramani, Matthew A. Hyde, Jalene V. Velazquez, Lauren E. Williamson, Pavlo Gilchuk, Robert H. Carnahan, Galit Alter, James E. Crowe, Alexander Bukreyev

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

Abstract

Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.

Original language	English (US)
Article number	871
Journal	Communications Biology
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s42003-024-06556-0
State	Published - Dec 2024
Externally published	Yes

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Ilinykh, P. A., Huang, K., Gunn, B. M., Kuzmina, N. A., Kedarinath, K., Jurado-Cobena, E., Zhou, F., Subramani, C., Hyde, M. A., Velazquez, J. V., Williamson, L. E., Gilchuk, P., Carnahan, R. H., Alter, G., Crowe, J. E., & Bukreyev, A. (2024). Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement. Communications Biology, 7(1), Article 871. https://doi.org/10.1038/s42003-024-06556-0

Ilinykh, PA, Huang, K, Gunn, BM, Kuzmina, NA, Kedarinath, K, Jurado-Cobena, E, Zhou, F, Subramani, C, Hyde, MA, Velazquez, JV, Williamson, LE, Gilchuk, P, Carnahan, RH, Alter, G, Crowe, JE & Bukreyev, A 2024, 'Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement', Communications Biology, vol. 7, no. 1, 871. https://doi.org/10.1038/s42003-024-06556-0

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title = "Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement",

abstract = "Antibodies to Ebola virus glycoprotein (EBOV GP) represent an important correlate of the vaccine efficiency and infection survival. Both neutralization and some of the Fc-mediated effects are known to contribute the protection conferred by antibodies of various epitope specificities. At the same time, the role of the complement system remains unclear. Here, we compare complement activation by two groups of representative monoclonal antibodies (mAbs) interacting with the glycan cap (GC) or the membrane-proximal external region (MPER) of GP. Binding of GC-specific mAbs to GP induces complement-dependent cytotoxicity (CDC) in the GP-expressing cell line via C3 deposition on GP in contrast to MPER-specific mAbs. In the mouse model of EBOV infection, depletion of the complement system leads to an impairment of protection exerted by one of the GC-specific, but not MPER-specific mAbs. Our data suggest that activation of the complement system represents an important mechanism of antiviral protection by GC antibodies.",

author = "Ilinykh, {Philipp A.} and Kai Huang and Gunn, {Bronwyn M.} and Kuzmina, {Natalia A.} and Kritika Kedarinath and Eduardo Jurado-Cobena and Fuchun Zhou and Chandru Subramani and Hyde, {Matthew A.} and Velazquez, {Jalene V.} and Williamson, {Lauren E.} and Pavlo Gilchuk and Carnahan, {Robert H.} and Galit Alter and Crowe, {James E.} and Alexander Bukreyev",

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doi = "10.1038/s42003-024-06556-0",

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AU - Ilinykh, Philipp A.

AU - Huang, Kai

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AU - Kedarinath, Kritika

AU - Jurado-Cobena, Eduardo

AU - Zhou, Fuchun

AU - Subramani, Chandru

AU - Hyde, Matthew A.

AU - Velazquez, Jalene V.

AU - Williamson, Lauren E.

AU - Gilchuk, Pavlo

AU - Carnahan, Robert H.

AU - Alter, Galit

AU - Crowe, James E.

AU - Bukreyev, Alexander

PY - 2024/12

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Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement

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