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

Autor: Ilinykh PA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Huang K; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Gunn BM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA., Kuzmina NA; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Kedarinath K; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Jurado-Cobena E; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Zhou F; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Subramani C; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Galveston National Laboratory, Galveston, TX, USA., Hyde MA; Galveston National Laboratory, Galveston, TX, USA., Velazquez JV; Paul G. Allen School of Global Health, Washington State University, Pullman, WA, USA., Williamson LE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Gilchuk P; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Carnahan RH; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA., Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. Galit.Alter@modernatx.com., Crowe JE Jr; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org., Bukreyev A; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. alexander.bukreyev@utmb.edu.; Galveston National Laboratory, Galveston, TX, USA. alexander.bukreyev@utmb.edu.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. alexander.bukreyev@utmb.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Jul 17; Vol. 7 (1), pp. 871. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1038/s42003-024-06556-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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