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Although mycoplasma infections cause massive economic losses in poultry, pigs, cattle and sheep rearing, currently no vaccines are available against many mycoplasma species that infect farm animals. One reason is that mycoplasmas are difficult to culture because they need a complex medium that contains animal serum. The serum is expensive, variable between lots, and can be contaminated with viruses.
The EU-funded MYCOSYNVAC project is designing a universal chassis vaccine to inoculate animals against several mycoplasma species and viral infections, which can be grown in a medium without animal components. The project team have also identified the components in the serum which are critical to produce a newly defined medium that can optimally sustain vaccine growth.
‘Even when effective vaccines are available, namely against Mycoplasma hyopneumoniae in pigs, and Mycoplasma gallisepticum and Mycoplasma synoviae in poultry, the complex media including animal serum makes the vaccine production process very irreproducible and prone to contamination by animal viruses,’ says project coordinator Luis Serrano, director of the Centre for Genomic Regulation (CRG) in Barcelona, Spain.
Reprogramming bacteria
‘We capitalise on our extensive systems biology knowledge of Mycoplasma pneumoniae and on cutting-edge synthetic biology methodologies to design a universal mycoplasma chassis that can be deployed as single or multi-vaccine in a range of animal hosts,’ Serrano explains.
Mycoplasma pneumoniae is an ideal starting point for designing a vaccine chassis as it has a small genome about which a great deal is known. However, these bacteria are not ideal for making vaccines because when inactivated by UV light or heat like traditional vaccines, many do not attach to the host’s epithelial cells and so fail to trigger the appropriate immune reaction.
One goal of MYCOSYNVAC therefore is to reprogramme mycoplasma to make it ‘semi-infectious’. That is, still capable of attaching to the host’s epithelial cells, but without causing cell damage or inflammatory responses typical of animal infections.
The project consortium is optimising the vaccine chassis for fast growth in an animal-serum-free medium. They are achieving this using innovative synthetic biology techniques, such as introducing a saturated fatty acid biosynthesis pathway into the chassis so that external sources of fatty acids are unnecessary.
It is also scaling up production in bioreactors to produce material for animal studies. These studies will assess efficacy against one or more pathogens (e.g. mycoplasma and viruses) in combinations with immunologic adjuvants to create a targeted vector vaccine.
Meeting industry needs
Ultimately, the aim is for large-scale production of broad-spectrum animal vaccines for industrial use. Without the need for an expensive medium containing animal serum, vaccines can be produced with dramatically reduced costs and increased reproducibility and safety.
Finding effective vaccines to treat animals infected with mycoplasmas is also particularly important because these bacteria are very small and lack a cell wall, which makes them resistant to many common antibiotics. The universal mycoplasma chassis will enable animals to be vaccinated against mycoplasma species, and potentially many other pathogens, avoiding the use of antibiotics.
‘By genome comparison, metabolic modelling and rationally engineering its genome, we are creating a vaccine chassis for industry. The process will be guided by the world’s second-largest industry in animal vaccination, as well as an SME specialising in peptide display and screening,’ says Serrano.
‘This will ensure the exploitation and commercialisation of our work and contribute to maintaining Europe’s privileged position in this field,’ he says. ‘Our ultimate goal is to meet the needs of the livestock industry, taking care of ethical issues, foreseeable risks, and preparing effective dissemination and training materials. Significant benefits are expected for the EU livestock industry, society, and for the field of synthetic biology.’