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ZAPI: Finding new ways to fight new zoonoses


Jean-Christophe Audonnet
Jean-Christophe Audonnet

Zoonoses, from the Greek ‘zoon’ (animal) and ‘nosos’ (sickness), are infectious diseases found in animals (usually vertebrates) that can be naturally transmitted to humans (or vice versa). Zoonoses occur relatively frequently and can be caused by viruses, bacteria, fungi and parasites. Diseases such as Ebola, SARS (severe acute respiratory syndrome), salmonellosis, anthrax, brucellosis, leptospirosis, plague, and influenza are all zoonoses. In 2016, the World Health Organisation (WHO) highlighted that about 75 % of new diseases that have affected humans over the last decade have been zoonotic, while 61 % of all human infectious diseases originated in animals. 

IMI’s Zoonosis Anticipation and Preparedness Initiative (ZAPI) project aims to respond quickly to the emergence of new zoonotic diseases by developing new processes for the production of medicines like vaccines and antibodies for animal and human health needs. As an adequate tool to control infectious diseases, vaccination is integral to protecting both animals and people, but is still under-used around the world.  The WHO's Immunisation Week, held every April, aims to raise awareness of the life-saving benefits of vaccines.

Expanding to human viral targets

‘We are developing the process of vaccine manufacturing, so we can show that at the end of the project it will be possible to manufacture a very high number of doses within a very limited timeline. The activity is to demonstrate that we can deliver control tools – therapeutic antibodies and/or vaccines – between 8 and 12 weeks after the identification of the pathogenic viruses,' explains ZAPI project coordinator Jean-Christophe Audonnet of Bio R&D, Merial S.A.S. (now part of Boehringer Ingelheim).

 ‘Right now we are in a critical phase to demonstrate the industrial feasibility of the steps that we have done at small scale with our academic partners. The main objectives of the project will be fulfilled, based on the viruses that we are using as models. The next step will be to expand that to some human viral targets, and that is why we have a number of contacts with different organisations, such as CEPI [Coalition for Epidemic Preparedness Innovations] or the Gates Foundation, who will potentially use the ZAPI methodology approach in their projects,’ says Dr Audonnet.

Scientists engaged in the 5-year collaboration between more than 20 European partners, including human and veterinary research institutions, NGOs (non-governmental organisations), regulatory experts, academic groups, producers of vaccines and biotechnological companies, are using three viruses as models. They have chosen Rift Valley Fever Virus (which can affect animals such as cows, sheep, goats, and camels, and is spread mostly by mosquitoes); Schmallenberg Virus (affects cattle, bison, sheep and goats, appears to be transmitted by midges); and Middle East Respiratory Syndrome Coronavirus (camels are detected as the primary source, although bats may be the ultimate reservoir of the virus).

Humans infected with Rift Valley Fever Virus can suffer fever, muscle pain, and week-long headaches, as well as loss of sight, bleeding, and liver problems. The disease is spread to people by direct or indirect contact with the blood or organs of infected animals, but also through the bite of infected mosquitoes. Schmallenberg Virus causes fever, diarrhoea, and reduced milk yield in adult cattle and malformations in newborns. There is no evidence of human infection reported, but related viruses have a clear zoonotic potential. Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is one of several viruses identified as a likely cause of a future epidemic in humans, causes severe lower respiratory tract disease. Since 2012, there have been 2 374 human cases of MERS-CoV infection across 27 countries, with a global death rate of 35 %.

Generation of neutralising antibodies

Over the past 70 years, more than 300 zoonotic diseases have been observed, and it is estimated that 631 000 to 827 000 unidentified viruses exist that have zoonotic potential.  Zoonotic diseases are responsible for over 2.7 million deaths and over 2.5 billion cases of human illness every year, and so represent a huge health and economic risk to both people and animals.

In its approach to the development of methods of rapid characterisation of new pathogenic viruses and the development of new vaccines and antibodies, ZAPI first turned to animals.  Dr Audonnet explains that the reason was simplicity and efficiency. ‘It is possible to use an animal model in an emergency when there is no time to do all the steps in human clinical trials. The demonstration of the capacity of a vaccine to induce protection will come from data generated in different animal species. We have now established the evidence that we can protect multiple target species (sheep, camels and llamas) and several small lab animal species, for the three model viruses that we are using in the ZAPI methodology project,’ says the ZAPI project coordinator. 

With the belief that the methodologies developed by ZAPI could spread globally as a general principle to developing vaccines under a ’One Health’ approach, in order to achieve optimal health for people, animals and the environment, Dr Audonnet highlights the generation of key neutralising antibodies against all three target model viruses. 

The overall aim of ZAPI is to develop a common pipeline for the rapid identification of key viral immunogens and corresponding neutralising reagents and their rapid and high-yield quality control production. Moreover, ZAPI aims to deliver the methodology for manufacturing subunit vaccines against at least two target viruses: Rift Valley Fever Virus and Schmallenberg Virus, as well as neutralising reagents against at least two target viruses (Middle East Respiratory Syndrome Coronavirus and Rift Valley Fever Virus).

’For fighting infectious viral diseases, one can use typically active immunisation (vaccination) for people and animals, but there is also the possibility to use passive immunisation in people in case of need. That is why ZAPI is addressing both: the need to prevent the disease with vaccines, but also when there is a highly acute or very infectious disease, spreading fast, the need to treat infected people in hospitals, and the “therapeutic antibodies” are the key tools for that. It can be difficult or very long to identify new active and safe antiviral drugs against a new virus, but if there is a possibility to generate and manufacture very rapidly antibodies, then good medical benefit can be provided to the patients. So the idea we have in ZAPI is to support a global approach with vaccines and neutralising antibodies, which can be used for therapeutic purposes in infected patients, but also prophylactically for exposed medical staff,’ concludes Dr Audonnet.

About World Immunisation Week

The WHO marks World Immunisation Week annually during the last week of April; in 2019, it runs from 24-30 April. Information on activities in Europe can be found on the websites of WHO Europe and the ECDC. To mark World Immunisation Week 2019, IMI is publishing a short series of articles on the results and activities of our vaccine projects.

Find out more about the ZAPI project