1. Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
- Author
-
European Commission, Innovative Medicines Initiative, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, Bosch, Berend Jan, European Commission, Innovative Medicines Initiative, European Federation of Pharmaceutical Industries and Associations, Ministerio de Economía y Competitividad (España), National Institutes of Health (US), China Scholarship Council, Widjaja, Ivy, Wang, Chengbao, Haperen, Rien van, Gutierrez-Alvarez, Francisco J., Dieren, Brenda van, Okba, Nisreen M. A., Stalin Raj, V., Li, Wentao, Fernandez-Delgado, Raúl, Grosveld, Frank, Kuppeveld, Frank J. M. van, Haagmans, Bart L., Enjuanes Sánchez, Luis, Drabek, Dubravka, and Bosch, Berend Jan
- Abstract
The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
- Published
- 2019