Community Research and Development Information Service - CORDIS

H2020

MycoSynVac Report Summary

Project ID: 634942
Funded under: H2020-EU.2.1.4.

Periodic Reporting for period 1 - MycoSynVac (Engineering of Mycoplasma pneumoniae as a broad-spectrum animal vaccine)

Reporting period: 2015-04-01 to 2016-03-31

Summary of the context and overall objectives of the project

Annually, infections caused by Mycoplasma species in poultry, cows, and pigs result in multimillion Euro 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 for which effective vaccines are available (namely, Mycoplasma hyopneumoniae in pigs and Mycoplasma gallisepticum and Mycoplasma synoviae in poultry), the production process of the vaccines is challenging.
The main aim of this project is to design a universal Mycoplasma chassis that can be deployed as single- or multi-vaccine in a range of animal hosts. 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).
To achieve this overarching goal, the MycoSynVac project has the following specific objectives: 1) Vaccine Design, 2) Chassis Engineering, and 3) Optimization of Large-Scale Production, all this taking into account the future exploitation of the technology developed and facing ethical concerns that synthetic biology can awaken.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since the start of the project in April 2015, all team members have significantly contributed to the project progress. The Consortium has performed a number of key actions and so far some results have been obtained:
Regarding the development of a whole-cell dynamic model of M. pneumoniae, we have already finished the model of glycolysis and have parameterized the key metabolic pathways. In the same way the workflows for the generation of the dynamic model are in place and a first constrain-based model of metabolism is being tested. Quantitative experimental data on metabolite and enzyme concentrations have been determined and used to calibrate the model.
On the chassis design, we have listed the essential proteins, identified the genes responsible of pathogenicity as well as, some genes involved in growth. Also, we have started the analysis of the elements that should be essential to allow growth and proliferation of the chassis in bioreactors. We are in the process of making constructs harboring several of the genes that when overexpressed make the bacteria grow faster to obtain a fast-dividing chassis.
Regarding the implementation of genome transplantation for genome engineering, the cloning the M. pneumoniae genome in yeast has been achieved. Related to tools for genome engineering, we have developed a system for homologous recombination and a cre-lox system that allows removal of the antibiotic resistance. This allows, in case genome transplantation will not work, the rational engineering of the chassis.
For the vaccine development, we have identified antigens and virulent factors, and we are currently building-up a new computational tool to predict potential membrane proteins and neutralizing epitopes. Simultaneously, we have done preliminary studies on infection challenges. These studies, performed in pigs and calves, demonstrate that we have suitable models for identifying virulence factors.
Since the project involves synthetic biology applied to animal health, we have also addressed the concerns that this may raise and its ethical implications. So far, we have reviewed literature in order to know the perception of using synthetic biology for producing animal vaccines. With this in mind, we are currently designing the forthcoming study on sociological perception that will be carried out in 5 European countries with focus groups of experts and lay-person.
An Innovation Board has been created with the aim to continuously monitor the project progress, identifying all exploitable results and being the responsible to envisage the commercial route for all of them. So far, some results, besides the vaccine which is the main result of the project, have been identified and discussion of how to take advantage of them has been initiated.
During this period, consortium has also made a big effort in dissemination. We have created the MycoSynVac visual identity, including some material such as the logo, the website, etc. For the time being we have organized a scientific cafe, the project has been presented in 3 international congresses and published 4 scientific articles with MycoSynVac acknowledgements, created a twitter account and we continue updating our web page. We have also started the preparation of a mobile scientific game that will help people to understand how vaccines work. All results, project activities and relevant information linked to the project were constantly updated on the project website, and made available to the scientific community as well as to the general public.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The MycoSynVac project is highly ambitious, as we are tackling a really disruptive approach to vaccine production: a universal chassis for vaccination based on M. pneumoniae able to grow efficiently and reproducibly in a defined serum-free medium.
The consortium brings together cutting-edge knowledge and resources on Mycoplasma, modeling, synthetic biology, antigen epitope determination and vaccine production and commercialization as well as other important areas such as dissemination and ethical aspects.
Overall, the activities performed during the first year of the project enabled us to lay the groundwork for a strong impact in several areas:
On the one hand, we are developing a new whole-cell model, which could be used to engineer the genome, define optimal medium and improve growth rates of different Mycoplasma species. An accurate whole-cell model capable of quantitative predictions will have a major impact in the systems and synthetic biology community.
We are engineering a bacterial cellular chassis. Based on a well-studied system such as M. pneumoniae, we are on the way to design a chassis that could be used not only as a vaccine (the main purpose of the project) but also for other therapeutic applications like lung infections, lung cancer or in cell reprogramming.
On the other hand, a Mycoplasma vaccine produced in a serum-free medium would be a breakthrough advance for MSD, helping them to maintain their leadership position. Similarly, validation of new technology based on the epitope screening system property of ATG, will help them to be a major players in the field.
Through dissemination and training, our Consortium is engaging with society and including all its activities in a wider setting than the restricted to biotechnology and veterinary research community. Indeed, we are highly conscious that the rise of synthetic biology has raised great concern, and for this reason we are undertaking different actions to publicize what SynBio really is and what contributions can make to society.
Finally, the project is promoting the collaboration between industry and academia. For dealing with such a complex problem, a strong collaboration is required and a continuous exchange of expertise and knowledge mandatory for the project success. In that sense, the strategic development plan of the project joins really challenging research developments carried out in academia and a commercial driven vision provided by the expertise of the industrial partners.

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