Identification of virulence factors as novel vaccine targets for contagious bovine pleuropneumonia by whole genome saturated mutagenesis
There is an urgent need for improved vaccines for contagious bovine pleuropneumonia (CBPP). CBPP is one of the most infectious and highly contagious diseases of cattle in Africa accounting for more than $38.8 million annual loss in cattle productivity in 12 endemic countries in sub-Saharan Africa. Currently, control of CBPP relies on a live vaccine of limited efficacy and occasional severe side effects. Achieving breakthroughs in developing effective tools, including vaccines, for CBPP intervention requires deeper insights into host-bacteria interactions.
Like other diseases caused by mycoplasma, CBPP is characterized by immunopathology, i.e. dysregulation of the host’s immune response. In vitro data indicates that this dysregulation begins at the very early stages of infection, at the initial site of bacteria-host cell interaction in the lung. We aim towards identifying vaccine candidates that can disrupt the bacteria-induced dysregulation of the host’s immune response.
To pump-prime this objective, we propose to generate a random mutant library of the bacteria which can be used to identify bacterial genes that play an important role in the initial bacteria-host cell encounters and the dysregulation of the host’s immune response. Within the scope of the initial project, we will use the mutant library in established in vitro assays to screen for bacteria that fail to induce the typical response (compared to the wild type bacteria). This will allow a deeper understanding of host-pathogen interactions, and the identified antigens will be tested in future in vivo experiments for their suitability as vaccine candidates.