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May 3rd, 2019
Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
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 ...

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.

DOI: 10.1080/22221751.2019.1597644
Emerging Microbes & Infections, 2019, 8:1, 516-530
Apr 26th, 2019
ZAPI: Finding new ways to fight new zoonoses
IMI

Zoonoses are infectious diseases that can be transmitted to humans from animals (and vice versa). IMI's ZAPI project is working to create new platforms and technologies that will facilitate a fast, coordinated, and practical response to new infectious diseases as soon as they emerge. In the run-up to World Immunisation Week 2019, the IMI Programme Office caught up with ZAPI project coordinator Jean-Christophe Audonnet for an update on the project's progress so far.

Aug 8th, 2018
Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection
V. Stalin Raj, Nisreen M. A. Okba, Javier Gutierrez-Alvarez, Dubravka Drabek, Brenda van Dieren, W. Widagdo, Mart M. Lamers, Ivy Widjaja, Raul Fernandez-Delgado, Isabel Sola, Albert Bensaid, Marion P. Koopmans, Joaquim Segalés, Albert Bensaid et al.

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause outbreaks in humans as a result of spillover events from dromedaries. In contrast to humans, MERS-CoV–exposed dromedaries develop only very mild infections and exceptionally potent virus-neutralizing antibody responses. These strong antibody responses may be caused by affinity maturation as a result of repeated exposure to the virus or by the fact that dromedaries—apart from conventional antibodies—have relatively unique, heavy chain–only antibodies (HCAbs). These HCAbs are devoid of light chains and have long complementarity-determining regions with unique epitope binding properties, allowing them to recognize and bind with high affinity to epitopes not recognized by conventional antibodies. Through direct cloning and expression of the variable heavy chains (VHHs) of HCAbs from the bone marrow of MERS-CoV–infected dromedaries, we identified several MERS-CoV–specific VHHs or nanobodies. In vitro, these VHHs efficiently blocked virus entry at picomolar concentrations. The selected VHHs bind with exceptionally high affinity to the receptor binding domain of the viral spike protein. Furthermore, camel/human chimeric HCAbs—composed of the camel VHH linked to a human Fc domain lacking the CH1 exon—had an extended half-life in the serum and protected mice against a lethal MERS-CoV challenge. HCAbs represent a promising alternative strategy to develop novel interventions not only for MERS-CoV but also for other emerging pathogens.

DOI: 10.1126/sciadv.aas9667
Science Advances Vol. 4, no. 8, eaas9667

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