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

ZAPI have put in place a new pan-virus methodology for ramping up the production of new vaccines in the next crisis

Image by Mike Mareen via Shutterstock
Image by Mike Mareen via Shutterstock

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. ZAPI 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.

“Consider the following scenario,” says Dr Jean-Christophe Audonnet who coordinated the IMI ZAPI project. “There is a disease outbreak among livestock. You need to control the disease at the source, and as soon as possible. The first approach will be based on veterinary sanitary measures which have been proven in the past: rapid diagnostic detection, mass culling of infected herds, and a strict ban of all transportation and movement in the infected area or region. If it is a zoonotic disease and infects humans, and especially if it is transmissible directly between people, then it becomes a ‘human disease outbreak’. Livestock are not likely to be vaccinated, as the objective at this stage will be to eliminate the source of virus.”

Dr Audonnet says that once the virus has been identified, work can immediately start on a vaccine for veterinary or human purposes, depending on the situation.

A methodology in three parts

The methodology essentially involves the use of three different ‘tools’. The first tool is the MPSP, which stands for Multimeric Protein Scaffold Particle, a kind of 3D structure that mimics the shape of a virus. The second tool is a bacterial superglue system made of two complementary elements: one being positioned on the scaffold particle, and the other being positioned on the third tool which is the specific immunogen subunit, designed from the pathogen that corresponds to the virus causing the outbreak. The MPSP and the immunogen subunit can then be assembled very simply through the combination of the two moieties of the superglue system.

“In essence, the ZAPI methodology is a kind of ‘open source’ system because it can be implemented in multiple ways,” explains Dr Audonnet. “From a regulatory perspective, the project is recommending one particular implementation: the MPSP, coupled with a particular way of using the bacterial superglue technology, and the expression of the immunogen subunit in the C1 fungus expression system.”  The C1 system is a fungus that can express very large amounts of recombinant proteins like vaccine subunits or antibodies, the manufacture of which can be rapidly scaled up in three to four months.

“We focused on the objective of achieving a surge vaccine manufacturing capacity corresponding to about 100 million doses four months after identification of a new viral pathogen. And this is why we used the E. coli system for manufacturing MPSP, and especially the Dyadic C1 fungus expression system for the immunogen subunit because it’s the only system able to deliver up to a few grams of immunogen subunits per litre of fermentation, fulfilling the objective for a very large capacity.”

“Nothing is absolutely mandatory except for the use of superglue. The elements can be changed if preferred, for instance different expression systems or a different MPSP can be used.”

 “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. 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 as in the ZAPI project, coupled to SARS-CoV-2 RBD subunit,” concludes Dr Audonnet.

Information about the outcomes of the ZAPI project will be disseminated through upcoming publications. Dr Jean-Christophe Audonnet is ZAPI Project Coordinator and is an employee of Boehringer Ingelheim Animal Health.

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