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.
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.
The availability of vaccines in response to newly emerging infections is impeded by the length of time it takes to design, manufacture, and evaluate vaccines for clinical use. Historically, the process of vaccine development through to licensure requires decades; however, clinicians and public health officials are often faced with outbreaks of viral diseases, sometimes of a pandemic nature that would require vaccines for adequate control. New viral diseases emerge from zoonotic and vectorborne sources, such as Middle East Respiratory Syndrome coronavirus and Chikungunya, and while these diseases are often detected in resource-rich countries, they usually begin in low- and mid-income countries.1 Therefore, part of the timeline for a vaccine involves surveillance and detection of new pathogens in remote areas and transfer of specimens to laboratories capable of vaccine development.