Zoonotic anticipation and preparedness initiative


Many infectious diseases, including influenza, coronaviruses and Ebola, can be transmitted to humans from animals (and vice-versa). Known as zoonoses, these diseases represent a serious threat to both human and animal health. ZAPI delivered a modular, platform-based process that allows the rapid development and manufacture of vaccines and antibodies to prevent and treat zoonoses. Crucially, their platform approach was integrated into the EU’s new Regulation on Veterinary Medicinal Products.

Zoonoses – a threat to human and animal health

Many infectious diseases, including influenza, Ebola, and coronaviruses such as SARS-CoV-2, can be transmitted to humans from animals (and vice-versa). Known as zoonoses, these diseases represent a serious threat to both human and animal health, and scientists estimate that more than 60% of human infectious diseases come from animals. New infectious diseases, many of them zoonoses, have been emerging at an increasing frequency around the world for a number of years. The COVID-19 pandemic showed just how fast a new disease can spread once it gets into the human population.

ZAPI was launched in 2015 with the goal of developing new methodology for the rapid development and manufacture of vaccines and neutralising antibodies within six months of the start of an outbreak of a new zoonotic disease.

The team focused on three viruses:

  • Rift Valley Fever virus causes recurrent outbreaks among ruminants (e.g. cattle, sheep and goats) and humans across large parts of the world. Infection can cause severe illness and/or death in animals and humans.
  • Schmallenberg virus is associated with abortions, stillbirths and malformations in ruminants in Asia, Africa, Oceania and (since 2011) Europe. No evidence of human infection has been reported but related viruses have zoonotic potential.
  • Middle East Respiratory Syndrome (MERS) coronavirus first emerged in the Arabian peninsula in 2012, causing severe lower respiratory tract disease in humans and killing around a third of reported patients. Dromedaries and camels are likely to be a major animal source of infection in humans. The virus that causes MERS is closely related to the SARS-CoV-2 virus that causes COVID-19.

Zoonoses clearly demonstrate that the health of the people is closely interlinked with the health of the animals and the environment – these types of diseases require a ‘One Health’ approach, and so the project included experts on both human and animal health.

The project achieved its goals of demonstrating the large-scale manufacture of both veterinary vaccines and antibodies for human use. What’s more, the project’s work on vaccines fed directly into the new Veterinary Medicinal Products Regulation.

Vaccines – a modular approach proves successful

On vaccines, the project came up with a modular, platform-based process that allows the rapid development and manufacture of vaccines for use in animals (on the basis that it is better to stop an outbreak while a virus is still limited to infecting animals, i.e. before it has crossed over into humans). Firstly, the project developed a set of multimeric protein scaffold particles (MPSPs), which can be coupled with different immunogen subunits (i.e. the part of the vaccine that is specific to the disease and triggers the immune response) to create a vaccine.

Meanwhile, the project also identified the elements of the different viruses that showed the most promise for use as the immunogen part of the vaccines.

The team then used a novel ‘bacterial superglue’ to attach the immunogen to the scaffold. Tests showed that Schmallenberg virus and Rift Valley Fever virus vaccines developed this way were successful at protecting cows and lambs from the respective diseases.

On the manufacture side, ZAPI developed and refined a fungus-based system brought into the project by SME partner Dyadic to generate high yields of the immunogen subunits. The MPSPs were produced using a system based on the bacteria Escherichia coli.

Advances on antibodies

The project succeeded in selecting and validating at least one lead antibody candidate for each of the viruses addressed by the project. In vivo tests confirmed that the antibodies do offer effective protection against disease. ZAPI also used a transient transfection expression platform to manufacture the antibodies at scale, without compromising the potency of the resulting antibodies.

Impacts on regulations

Once a vaccine has been developed, it still needs to be approved by the relevant regulatory authorities, and here ZAPI came up with a solution – the Platform Technological Master File (PTMF), the principle of which was integrated into the EU’s new Regulation on Veterinary Medicinal Products (Regulation (EU) 2019/6). Under the PTMF concept, the parts of the file relating to the platform technology (such as the MPSPs used by ZAPI) would only have to be approved by regulators once. Once the platform part is approved, vaccine developers would only have to fill in the parts of the form relating to the new antigen. So for example, if a vaccine made up of an MPSP plus a Rift Valley Fever vaccine is approved, preparing a dossier and getting approval for a vaccine made up of an MPSP plus a MERS antigen would be much quicker and cost less.

ZAPI’s approach also received interest from the European Medicines Agency for its possible application for immunological medicinal products for human use.


The project leaves behind an impressive legacy. The wealth of scientific and industrial knowledge generated has been shared via publications in scientific journals and presentations and posters at conferences. ZAPI’s learnings are also part of two university courses on vaccines.

Thanks to ZAPI, SME Dyadic was able to further improve its C1 fungus-based system for the production of antigens, and is using the system for the development of the potential next generation coronavirus vaccine candidates, among other things. Another SME in the project, Harbour Biomed, has filed a patent application for the therapeutic monoclonal antibody against MERS. A similar approach was used for the development of monoclonal antibodies against COVID-19 as part of a Horizon 2020 project.

Other outcomes of ZAPI have been picked up by the IMI COVID-19 project CARE.

Achievements & News

Surge vaccine production principles now written into EU law

Bringing a new vaccine to market takes a long time in part because manufacturers have to prove that their vaccines are beyond reproach, safety-wise. In recent years, pharma companies have been experimenting with ‘platform technologies’ that can speed up this lengthy licensing process. Platform technologies refer to any technology, whether it’s a mechanism, delivery method, or cell line, that we can use as a base for producing different medicinal products.###

IMI’s ZAPI project, recognising that such a platform is essential in the face of the threat of emerging zoonotic disease outbreaks, started working on a plug-and-play vaccine and antibody production platform in 2015. Their platform allows the immunogen of a new virus to be plugged in to produce millions of doses of new doses within months.

The ZAPI partners not only built the technical platform (and put it into practice when COVID-19 struck), they also worked the regulatory side. Now, they have influenced the updated legislative guidelines for veterinary medicine products that will be applicable in all EU countries from 28 January 2022, thus likely shaving years off future authorisation applications.

'That means that there is no need in the licensing procedure to re-discuss the safety of the platform. It’s done,' says Dr Joris Vandeputte, president of the International Alliance for Biological Standardization (IABS). The vaccine developer only has to insert the new immunogen for the new disease, and then go on with final product testing.

'This is really incommensurable, what ZAPI has done here. The big added value is not only the principle, it's also the fact that we have prepared the regulatory authorities. We are sure that thanks to this technology, in six months we can generate not millions, but billions of the antigens needed for vaccines.'

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A recipe for the next disaster: a new, pan-virus methodology for ramping up vaccine production

One way of dealing with the threat of another pandemic like COVID-19 is investing in plug-and-play vaccine technologies that can respond to a wide variety of virus types. IMI’s ZAPI project has created a new methodology for quickly designing and manufacturing a vaccine in the event of a new disease outbreak in humans or animals that consists of the assembly of only two components. ###The only variable is the immunogen, which will change depending on the target pathogen.

Manufacture of a so-called ‘ZAPI-like vaccine’ can take place anywhere. That’s because a guiding objective in the design of the manufacturing process was to keep it very simple by limiting the number of steps involved. Having multiple manufacturing sites is one of the key factors in responding as quickly as possible in the event of a new pandemic as it enables to expand production capacity close to the needs everywhere in the world.

‘We have demonstrated up to a significant scale that this vaccine approach can be readily and rapidly industrialised to supply the large number of vaccine doses which are needed,’ explains ZAPI coordinator Jean-Christophe Audonnet. ‘This is something that everyone can appreciate when you see that SARS-CoV-2 vaccine manufacturers are suffering from shortages or significant capacity reductions compared to the amounts that had been promised initially in the vaccine supply agreements.’

ZAPI-based vaccines are currently being developed for SARS-CoV-2. 'Chinese, UK and US teams are actively working with this MPSP display-based vaccines, most of them using exactly the same MPSP [multimeric protein scaffold particle] as in the ZAPI project, coupled to SARS-CoV-2 RBD subunit,' concludes Dr Audonnet.

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IMI’s ZAPI project: ‘This is like a real-life experiment for us’

Zoonotic diseases are those that are transmitted from animals to humans. COVID-19 is zoonotic in origin, and experts believe such outbreaks could become increasingly frequent in the future. 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 diseases. Much of the project’s work on the Middle East respiratory syndrome (MERS) coronavirus, can be directly applied to SARS-CoV-2, the virus that causes COVID-19, as the two are closely related.

‘This scenario with COVID-19 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,’ says project coordinator Jean-Christophe Audonnet of Boehringer Ingelheim.

‘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,’ he continues. ‘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. Maybe we have to reflect all together as a society how to overcome this.’

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COVID-19 is a sign of the times – an opinion piece by IMI’s Pierre Meulien

This month IMI announced a new funding Call in reaction to the spread of COVID-19. The process is being fast-tracked, just like the call for Ebola projects in 2014. However, as IMI Executive Director Pierre Meulien points out in a new opinion piece published on the IMI website, there’s nothing unexpected about the emergence of these epidemics.###

‘Every year, viruses jump from animals to the human population, including certain strains of influenza,’ he writes. ‘The closer we live to animals, the more of these ‘jumps’ we’re going to see.’

The scientific community needs to get ready to respond regardless of where the next virus comes from. In that respect, two ongoing IMI projects now look particularly prescient: the ZAPI project was set up to deliver a platform and technologies to facilitate a rapid response to future disease outbreaks. In 2019, the project demonstrated that certain antibodies can stop the MERS coronavirus from infecting new cells, and they’re now assessing whether the antibodies could also be effective against SARS-CoV-2, the virus that causes COVID-19. COMBACTE-NET, part of the antimicrobial resistance programme, has set up a network of clinical and laboratory sites across Europe that has been mobilised to support global efforts to standardise the information gathered from patients with suspected or confirmed COVID-19.

COVID-19 has put everyone on the alert because there’s so much we don’t know about it. Dr Meulien concludes: ‘In the coming months, the scientific community will no doubt be able to answer more questions about the epidemiology and modes of transmission of the virus, and the story will gradually recede from the headlines. Meanwhile, the projects that will result from the IMI coronavirus call will outlast the news cycle, putting everything in place for the next outbreaks, wherever or however they may emerge.’

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IMI’s vaccine projects in the spotlight

In the run-up to World Immunisation Week 2019, the IMI Programme Office caught up with three projects working in this important area.###

  • Vaccines are one of the most effective public health measures out, yet public distrust in immunisation programmes is limiting high vaccine uptake, resulting in outbreaks of vaccine-preventable infectious diseases that had almost disappeared. ADVANCE has paved the way for an open system for actively monitoring vaccine coverage, benefits and risks in Europe. Read more
  • 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. Read more
  • Every year, pharmaceutical companies develop vaccines designed specifically to combat the strains of influenza (flu) that are most likely to be in circulation the following winter. However, accurately predicting how much protection a new vaccine would actually offer against emerging virus types is far from easy. The FLUCOP project is developing tools to address this challenge. Read more

World Immunisation Week is organised by the World Health Organization at the end of April every year.


  Show participants on map
EFPIA companies
  • Astrazeneca AB, Södertälje, Sweden
  • Boehringer Ingelheim Animal Health France, Lyon, France
  • Boehringer Ingelheim Vetmedica GMBH, Ingelheim am Rhein, Germany
Universities, research organisations, public bodies, non-profit groups
  • Academisch Ziekenhuis Leiden, Leiden, Netherlands
  • Agencia Estatal Consejo Superior De Investigaciones Cientificas, Madrid, Spain
  • Association Internationale De Standardisation Biologique Pour L'Europe (IABS-EU), Lyon, France
  • Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
  • Friedrich Loeffler Institut - Bundesforschungsinstitut Fuer Tiergesundheit, Greifswald-Insel Riems, Germany
  • Institut De Recerca I Tecnologia Agroalimentaries, Caldes De Montbui- Barcelona, Spain
  • Institut Pasteur, Paris, France
  • Stichting Wageningen Research, Wageningen, Netherlands
  • Stiftung Tieraerztliche Hochschule Hannover, Hannover, Germany
  • Universitatsklinikum Bonn, Bonn, Germany
  • Universite D'Aix Marseille, Marseille, France
  • Universiteit Utrecht, Utrecht, Netherlands
Small and medium-sized enterprises (SMEs)
  • Artemis Bio-Support B.V., Utrecht, Netherlands
  • Dyadic Nederland BV, Wageningen, Netherlands
  • Finovatis, Lyon, France
  • Harbour Antibodies BV, Rotterdam, Netherlands
  • Viroclinics Biosciences BV, Rotterdam, Netherlands

NameEU funding in €
Academisch Ziekenhuis Leiden715 500
Agencia Estatal Consejo Superior De Investigaciones Cientificas416 917
Artemis Bio-Support B.V.696 425
Association Internationale De Standardisation Biologique Pour L'Europe (IABS-EU)318 800
Dyadic Nederland BV403 650
Erasmus Universitair Medisch Centrum Rotterdam1 090 735
Friedrich Loeffler Institut - Bundesforschungsinstitut Fuer Tiergesundheit1 293 350
Harbour Antibodies BV173 700
Institut De Recerca I Tecnologia Agroalimentaries730 467
Institut Pasteur192 600
Stichting Wageningen Research1 390 269
Stiftung Tieraerztliche Hochschule Hannover747 000
Universitatsklinikum Bonn194 400
Universite D'Aix Marseille195 570
Universiteit Utrecht829 305
Viroclinics Biosciences BV150 000
Total Cost9 538 688