Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection

• Published in: Cell Vol. 164; no. 3; pp. 392 - 405
• Main Authors: Flyak, Andrew I., Shen, Xiaoli, Murin, Charles D., Turner, Hannah L., David, Joshua A., Fusco, Marnie L., Lampley, Rebecca, Kose, Nurgun, Ilinykh, Philipp A., Kuzmina, Natalia, Branchizio, Andre, King, Hannah, Brown, Leland, Bryan, Christopher, Davidson, Edgar, Doranz, Benjamin J., Slaughter, James C., Sapparapu, Gopal, Klages, Curtis, Ksiazek, Thomas G., Saphire, Erica Ollmann, Ward, Andrew B., Bukreyev, Alexander, Crowe, James E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.01.2016
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Cross Reactions; Disease Models, Animal; Ebolavirus - immunology; Epitope Mapping; Guinea Pigs; Hemorrhagic Fever, Ebola - immunology; Humans; Mice; Mice, Inbred BALB C; Microscopy, Electron; Models, Molecular; Mutagenesis; Survivors; Uganda; Uganda
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2015.12.022

Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections. [Display omitted] •Natural Ebolavirus infection induced B cells encoding cross-reactive antibodies•Some cross-reactive human antibodies neutralized multiple Ebolavirus species•A large proportion of BDBV-neutralizing antibodies bound to the glycan cap•Glycan cap-specific antibodies exhibited very potent neutralizing activity Natural Ebola virus infection causes the induction of B cells that encode potent neutralizing human antibodies, which possess, in some cases, a surprising level of cross-reactivity for multiple species of filoviruses. The neutralizing antibody repertoire recognizes diverse features on the surface glycoprotein, but most of the potent antibodies recognize the glycan cap region.