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Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

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posted on 19.12.2019 by Ivy Widjaja, Chunyan Wang, Rien van Haperen, Javier Gutiérrez-Álvarez, Brenda van Dieren, Nisreen M.A. Okba, V. Stalin Raj, Wentao Li, Raul Fernandez-Delgado, Frank Grosveld, Frank J. M. van Kuppeveld, Bart L. Haagmans, Luis Enjuanes, Dubravka Drabek, Berend-Jan Bosch

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.

Funding

This study was financed by a grant from the IMI-ZAPI (Zoonotic Anticipation and Preparedness Initiative (ZAPI) project; Innovative Medicines Initiative (IMI)) [grant agreement no. 115760], with the assistance and financial support of IMI and the European Commission, and in-kind contributions from European Federation of Pharmaceutical Industries and Associations partners. This study was also partially financed by grants from the Ministry of Science and Innovation of Spain (BIO2016-75549-R AEI/FEDER, UE) and NIH (2PO1AIO6O699). This work was supported by Center for Scientific Review, China Scholarship Council.

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