A universal bacterial chassis for vaccination purposes based on Mycoplasma pneumoniae
Annually, infections caused by Mycoplasma species in poultry, cows, and pigs result in multimillion losses in the USA and Europe. There is no effective vaccination against many Mycoplasmas that infect pets, humans and farm animals (e.g. Mycoplasma bovis cow infection). Furthermore, most Mycoplasmas are difficult to grow in axenic culture, requiring a complex media that includes animal serum. Consequently, even in those cases in which effective vaccines are available (namely. M. hyopneumoniae in pigs and M. gallisepticum and M. synoviae in poultry), the production process of the vaccines is challenging.
Based on our extensive system biology knowledge of M. pneumoniae and on cutting-edge synthetic biology methodologies, we will design a universal Mycoplasma chassis that can be deployed as single or multi-vaccine in a range of animal hosts. We envision an iterative workflow that is (whole-cell) model-driven and relies on a range of genome-editing and transplantation tools, circuit (re-)design and chassis plug-in as well as on assessment of vaccine performance in pigs in an industrial setting. The chassis will be free of virulence determinants from M. pneumoniae and will be optimized for fast growth in a serum-free medium. Using this chassis, we will express heterologous antigens from one or more pathogens (i.e. Mycoplasma and virus) and biological adjuvants to create a targeted vector vaccine.
Speciﬁcally in this project we will target the development of attenuated and/or inactivated vaccine(s) against two Mycoplasma pathogens: M. hyopneumoniae (pigs) and M. bovis (cattle), and a combined one against M. hyopneumoniae and PRSSV virus (pigs). Last but not least, we will ensure that foreseeable risks are avoided, all ethical issues are handled in a transparent manner, and that our results and their implications are disseminated effectively and communicated efﬁciently with the European public.