Genomics for rational autogenous vaccine design to control Campylobacter infection in poultry

Campylobacter is the leading cause of food-borne gastroenteritis worldwide and the most common cause of infection in humans have been linked to the consumption of contaminated poultry meat. Previous poultry vaccines have provided short term reduction in Campylobacter intestinal load in chickens but have limited commercial efficacy because of high diversity and rapid evolution of strains. Genome-wide association study (GWAS) of isolates from humans and chicken have identified genes associated with survival of Campylobacter through the poultry processing chain. These genes represent targets for vaccine design that would be selectively neutral within the chicken gut and therefore could be sustained in the population. We designed an autogenous vaccine based on isolates with survival-associated genes and monitored the efficacy in the chicken and through processing. First, we sampled for Campylobacter across five broiler farms feeding into one abattoir in Norfolk and characterized genomic diversity using next generation sequencing (NGS), including the identification of survival genes. These data were then used in a predictive model to identify the minimum number of strains to be used in vaccine design based on known immunogenicity of the strains. Second, the vaccine was developed and given at two time-points to a whole farm of breeder chickens. Third, vaccine efficacy was monitored at three time points post-vaccination in vaccinated breeders and their progeny. The cfu/g reduction in the ceacum and neck skin were determined. This study demonstrates the potential for NGS in autogenous vaccine design to reduce harmful strains of bacteria that are carried commensally in livestock.