ATG bioinformatics help engineer mycoplasma bacteria for new vaccine platform

Merzhausen, Germany: – German-based clinical research organization ATG:biosynthetics has contributed its expertise in functional bioinformatics to a Europe-wide project that has combined gene engineering and biotechnology to design new vaccines based on the bacterium Mycoplasma pneumoniae.

ATG is a member of the MycoSynVac consortium undertaking an €8m EU-funded five-year project that was launched in May 2015 at the Centre for Genomic Regulation (CRG) in Barcelona.

The Spanish-co-ordinated project, undertaken under the EU’s Horizon 2020 (H2020) Research and Innovation program, also involves industrial and academic partners in UK, Germany, Denmark, The Netherlands, France, and Austria.

Cutting edge synthetic biology

The project combines systems biology with advanced synthetic biology methodologies to enable researchers to engineer a universal Mycoplasma bacterium chassis that will be optimized for fast and contamination-free growth.

The new chassis will be used to create vaccines targeting two highly detrimental pathogens that cause livestock animal suffering, with significant costs to the livestock industry. It is hoped it will also provide a platform for further applications, such as combating infectious lung diseases.

Using ATG peptide library

“The role of ATG:biosynthetics in this project has been of crucial importance for the success of the vaccine design,” said ATG’s CEO, Dr. Hubert S. Bernauer.

ATG’s Lab Head/Project Manager Adrien Eberlin, PhD, added, “We have had to identify new epitopes at the surface of M. hyopneumoniae, M.bovis and M.gallisepticum that will constitute new targets for the host immune system. The difficulty of this task relies on the complexity of our peptide library to handle to identify the numerous strategies that have been selected by mycoplasmas throughout evolution to escape the host immune system.”

“To fulfill this challenging mission, we have needed to combine our bioinformatic expertise with PepID technology for epitope mapping,” he added.

Overcoming mycoplasma barrier

Mycoplasmas infect animals and humans, with very few effective vaccines developed so far. Researchers have struggled to overcome the difficulty in growing most mycoplasmas in isolation from other organisms, requiring complex media that include animal serum. Thus, even where effective vaccines are available, they are hard to produce, with the process resistant to scale up and highly susceptible to viral contamination.

MycoSynVac seeks to harness extensive systems biology knowledge about M. pneumoniae and cutting-edge synthetic biology methodologies to design a universal Mycoplasma ‘chassis’ bacterium that will grow efficiently in a serum-free medium, to significantly improve production, quality, and efficiency. Resulting single- or multi-vaccine products can then be deployed in a range of animal hosts.

About ATG: biosynthetics

Advanced Technical Genetomics (ATG) is a German-based company that specializes in synthetic biology, combinatorial gene design and multi-gene expression. Located in Merzhausen near Freiburg, ATG offers a complete range of multi-gene and multi-peptide expression products and services for synthetic and molecular biology as well as allied research and development areas.

ATG: biosynthetics possesses particular strengths in designing tailor-made solutions (e.g., gene cluster and complete pathway designs) that harness its technologies and services in related product areas that include gene synthesis, bioinformatics, molecular in silico biodesign, epitope mapping and pathway engineering. These provide clients with individual products and services or integrated solutions that offer a complete product & service package for peptide/gene expression and synthetic biology applications.

ATG seeks partnerships and outsourcing projects that aim at developing and marketing high-potential applications, e.g. creating high efficiency DNA- and protein-based vaccines.

About MycoSynVac

The Mycosplasma bacteria are the smallest self-replicating organisms. Their lack of cell wall make them resistant to almost all antibiotics. Infections caused by Mycoplasma in livestock result in annual multimillion losses around the world. Although there are vaccines against two species of Mycoplasma that affect pigs and poultry, no vaccines exist for those Mycoplasma species that affect not only livestock but also pets and humans.

The new H2020 EU project MycoSynVac aims to bio-engineer Mycoplasma pneumoniae into a universal chassis for vaccination by using cutting-edge synthetic biology methodologies.

“We will engineer a new bacteria to be used as a vaccine, explains Luis Serrano, director of the Centre for Genomic Regulation (CRG), who his one of the project co-ordinators. “We will remove the genes that make the bacteria pathogenic and then improve the chassis for an optimized growth in a serum-free medium. By expressing specific harmless antigens from one or more pathogens, we will be able to create targeted vector vaccines.”

“We have been working for a long time to deeply understand Mycoplasma pneumoniae and are now ready to take a step forward and use this knowledge for the benefit of society”, adds Maria Lluch, staff scientist at the CRG and scientific co-coordinator of MycoSynVac.

A second phase of this project includes targeting the development of attenuated (with the pathogen weaken but still alive) and/or inactivated vaccines (with killed pathogen) against M. hyopneumoniae, which infects pigs, and M. bovis, which infects cattle.

The project pursues an ambitious challenge that requires both technical details but also societal and ethical dimensions to be taken into account.

To effectively address these highly diverse aspects, the project consortium is composed of: research groups working on gene engineering and design of biological systems at the CRG (Barcelona, Spain), the French National Institute for Agricultural Research (Bordeaux, France), Wageningen University ( The Netherlands), and Imperial College (London, UK), along with a research group focused on bioethical aspects from University of Copenhagen (Denmark); industrial partners of MSD Animal Health (Boxmeer, The Netherlands) and ATG Biosynthetics, along with risk assessment and public engagement experts Biofaction (Vienna, Austria).