Mycoplasmas are a type of bacteria that lack a cell wall. They can infect almost all living systems from plants to mammals, with each mycoplasma species specifically adapted to its host. “One of the biggest health challenges is that these bacteria are resistant to medication that would typically target the cell wall, such as penicillin-derived antibiotics,” explains MycoSynVac project coordinator Luis Serrano, Director of the Centre for Genomic Regulation in Spain. “This means they are difficult to eliminate and can cause lesions in infected animals that prevent their use for food.” For the majority of mycoplasma infections, there is no effective commercial vaccine, something that has implications for both Europe’s economy and health. In Europe alone, the mycoplasma pathogen M. bovis costs the cattle industry close to EUR 144 million per year. The lack of a vaccine also means that many large poultry plants resort to using antibiotics, which can lead to antibiotic-resistant pathogens that can adversely affect both animals and humans.
A universal vaccine
“We saw that there was a clear need for new and better vaccines against mycoplasma,” says Serrano. “Our aim in this project was to design a universal vector that could be deployed as a single- or multi-target vaccine in a range of animal hosts.” Universal vectors are designed to stimulate the immune system against multiple pathogen strains. In this case, the team successfully engineered a harmless version of a bacterium that colonises the human lung, called Mycoplasma pneumoniae. This became the project’s universal vector for animal vaccination. The idea was that surface proteins from other mycoplasma species can simply be ‘plugged in’ to the vector, and used as a vaccine. The non-pathogenic bacterial vaccine developed through the project has since been tested against a range of animal pathogens, with positive results. The solution has the potential to reduce livestock infections, and thus remove the need for antibiotics and other medical substances along the food chain. The team is currently evaluating the degree of protection against infection.
Tackling pneumonia in humans
There is an interesting twist to the story. Since completion of the project in March 2020, Serrano and his team have been looking to use the engineered vector to treat ventilator-associated pneumonia (VAP) in humans. This is a type of lung infection that affects patients on mechanical ventilation machines in intensive care units. The results achieved in MycoSynVac are being vigorously pursued in the context of the global fight against coronavirus. “We are currently exploring the possibility of applying the tools and techniques we developed in this project to block virus entry to the lung,” says Serrano. “For example, by engineering mutations in the protein used by coronavirus SARS-CoV-2, the virus could potentially be stopped from binding to lung cells.” The bacterial vector could then be used to express the target protein in patients not responding to conventional therapy, thus helping to block the virus. This work is currently ongoing. The Centre for Genomic Regulation has filed several patents, and recently launched a company to specifically target the treatment of human lung diseases.
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