ZAPI is laying the groundwork for the response to zoonotic disease outbreaks like COVID-19
Zoonotic diseases are those that are transmitted from animals (usually vertebrates) to humans. The coronavirus disease (COVID19) that started circulating in the human population in late 2019 is zoonotic in origin, and experts believe such outbreaks could become increasingly frequent in the future.
Jean-Christophe Audonnet coordinates the IMI-funded ZAPI project, which is actively working on preparing for such outbreaks. “Contacts with wild fauna are increasing as the population develops worldwide. In China, especially, there are a number of factors that are favourable to the emergence of these diseases. In Africa, as the economy develops, we are likely to see more, too.” He adds that in the case of the coronavirus that apparently originated in Wuhan, China, it’s actually the second time this type of virus has emerged.
Vaccines and monoclonal antibodies
The best we can do - and must do - is be prepared. In 2015, IMI launched ZAPI (Zoonotic Anticipation and Preparedness Initiative) to set up tools and platforms that would be ready to put into production for vaccines and monoclonal antibodies (cloned copies of the body’s natural defences) to efficiently counter emerging or remerging coronaviruses. “The objective is to demonstrate that we can deliver on these platforms, using three different prototype models of diseases that occurred in the recent past and which are zoonotic in nature.” The viruses that were used as models are Middle East respiratory syndrome coronavirus (MERS-CoV), Schmallenberg virus, and Rift Valley Fever. MERS-CoV and SARS-CoV-2, the virus that causes the COVID-19 pandemic at present, are genetically related.
"...the ZAPI system design is flexible enough to address about 90% of all the targets that we can face.”
Jean Christophe says, “A platform is a generic methodology or technology that can be used for multiple targets; in the case of vaccines, the only thing that will change will be the immunogen. It's an assembly of different components, so the way we manufacture the vaccine will always be the same.” He says the likelihood of producing a design that works for any new virus is unlikely. “It would be unwise to assume anyone could produce technology that can address every single case, but the ZAPI system design is flexible enough to address about 90% of all the targets that we can face.”
“It’s important to state that, in the ZAPI project, the primary focus is to develop vaccines for domestic animals, to protect these animals from disease and lower or block the risk of transmission to humans,” says virologist Bart L Haagmans of Erasmus Medical Centre, Rotterdam. “A unique feature of this project is that it combines animal health and human health so it includes veterinarians, physicians and scientists. At the moment, we are more focussed on animal intervention, but eventually these technologies could be used to develop human vaccines because the platform can address both needs.”
The scenario we are trying to prevent
The work of the ZAPI project is ongoing, but within the project work is restricted to the original three viruses. However, there are several outcomes based on the MERS-CoV model that can be directly applied to SARS-CoV-2, the virus that causes COVID-19. “Both in terms of therapeutic antibodies, which would be the priority, and in terms of a specific SARS-CoV-2 vaccine,” says Jean-Christophe. ZAPI researchers are also studying the potential of nanobodies, which are specific, genetically-engineered small antibodies, discovered in camels, dromedaries and llamas.
“We are ready to go for antibodies if the manufacturing is done using a CHO cell line (Chinese hamster ovary cell, commonly used for the production of protein therapeutics), says Jean-Christophe. “We are in the process of demonstrating the scalability of the vaccine platforms, which are based on the C1 system from ZAPI partner Dyadic." The C1 system is a fungus that can express very large amounts of recombinant proteins like vaccine subunits and antibodies, the manufacture of which can be rapidly scaled up (read more on the Dyadic website) . "We are also demonstrating the scalability of the manufacturing platform for antibodies, but they are quite new, and, as of today, vaccines or antibodies based on these platforms have not been evaluated in humans. But one can expect that the regulatory acceptance for innovative approaches will be changing after this SARS-CoV-2 outbreak crisis.”
“This scenario with COVID19 is exactly the scenario that we are working to prevent in the future – of course it’s never exactly the same virus but one of our models, the MERS coronavirus that occurred a few years ago, has taught us a lot about how to design and manufacture antibodies and to test them.”
Demonstrating what's technically possible
“As we have seen, the diseases are coming very fast, and it’s very difficult to react very efficiently to the different factors. We want to show, however, what is technically possible. It will depend on the exact type of disease and virus and that’s why we are ‘by design’ flexible in our ZAPI approach. In this way, we can create either vaccines or therapeutic antibodies - or both - depending on the situation. You have to consider the epidemiological data of each situation and adapt in real time.”
“It’s a real life experiment now for us. A factor that we need to explore better through dialogue is how we can reduce the timelines for the key decisions - political and regulatory ones. The regulations are designed to protect the safety of patients and that’s totally expected for standard products to be used in peace time. But when you need to act very quickly in ‘war time’, maybe we have to reflect all together as a society how to overcome this.”
Jean-Christophe Audonnet is ZAPI Project co-cooordinator at Boehringer Ingelheim
Bart Haagmans is a virologist at the Erasmus Medical Center in Rotterdam and co-coordinator of the ZAPI project.
This article was updated on 30/03/20.
COVID-19 is a sign of the times