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 mainly focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. 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.
Berend Jan Bosch
Interrogating humoral immune responses to find key protective antibodies against coronaviruses
Ivy Widjaja1, Chunyan Wang1, Rien van Haperen2,3, Javier Gutiérrez-Álvarez4, Brenda van Dieren1, Nisreen M.A. Okba2, V. Stalin Raj2, Wentao Li1, Raul Fernandez-Delgado4, Frank Grosveld2,3, Frank J.M. van Kuppeveld1, Bart L. Haagmans2, Luis Enjuanes4, Dubravka Drabek2,3 and Berend-Jan Bosch1
1 Utrecht University - Veterinary Medicine, Utrecht, the Netherlands
2 Erasmus Medical Centre, Rotterdam, the Netherlands
3 Harbour Antibodies B.V., Rotterdam, the Netherlands
4 National Center for Biotechnology - Spanish National Research Council, Madrid, Spain