National Agriculture and Food Research Organization (NARO) has developed the world's first method for rationally designing live vaccines in a short period of time. Using Erysipelothrix rhusiopathiae as a model, we estimated the genes involved in pathogenicity from the genomic information, and by deleting the genes, the bacteria was rationally attenuated. It is expected that this method can save labor in the development of live bacterial vaccines, which has been very costly and time-consuming.
Overview
The most effective way to prevent infectious diseases is to use effective vaccines in addition to thorough breeding hygiene management. However, developing a new vaccine is enormously costly and time-consuming. Most live vaccines, especially those used for livestock and poultry, are attenuated by random mutations in the genome through repeated culture and passaging of pathogens in animal species and/or cells that differ from the natural host, or in the presence of substances that cause changes in the DNA sequence or structure. Hence, in many cases the attenuation mechanisms in these live vaccines are unknown. Also, it has been pointed out that some live vaccines have safety issues, such as the risk of reversion to virulence.
For developing a safe and effective live bacterial vaccine, it is necessary to first analyze the large number of genes present in the genome of the pathogen and their expression regulation mechanisms. Then we must identify virulence genes and theoretically attenuate them by gene deletion or introducing mutations. However, it requires considerable time and effort to identify virulence genes and therefore it is extremely difficult to produce an excellent live vaccine in a short period of time.
NARO selected only genes involved in amino acid synthesis from the genomic information of Erysipelothrix rhusiopathiae which was used as a model. After identifying genes whose expressions is enhanced when this bacterium infects mouse immune cells (macrophages), genes were deleted from the genome. By this method we succeeded in developing attenuated vaccine candidate strains for the first time in the world. This method may be particularly effective in bacteria that exhibit a genetic trait called "genome reduction" and is expected to enable the identification of virulence genes in many bacteria.
Publication
Microbiology Spectrum, 2022, https://doi.org/10.1128/spectrum.03776-22
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