Dissection of protective responses to heterologous Campylobacter vaccines

Campylobacter jejuni is the largest cause of bacterial food borne zoonoses. There is a strong link between poultry, which are colonised to a high level by Campylobacter, and human disease. The ability to reduce Campylobacter in chickens by vaccination would greatly reduce human infection. Recently it has been shown that a Salmonella vaccine which presents a specific Campylobacter protein (CjaA), to the chicken immune system can protect against Campylobacter colonisation. CjaA is a transporter of amino-acids and we have identified several other similar transporters as candidates for vaccines. We have shown these are expressed when Campylobacter is in the intestines of the chicken. We will create vaccines where Salmonella expresses these other transport proteins and test them for protection. The reason why the CjaA vaccine works is not clear. The Salmonella strain that is used to present CjaA to the chicken vaccine still possesses some virulence traits which may drive the development of immunity. We will investigate the role of Salmonella vaccine strains which vary in their virulence, in the development of the immune response against CjaA. The understanding of the role of the Salmonella virulence properties in function of the vaccine will allow the development of improved strategies for control of Campylobacter. Joint with BB/D000866/1.

This project will investigate adaptive immunity in the control of Campylobacter. Recently it has been shown that a Salmonella vaccine which presents a specific Campylobacter protein (CjaA), to the chicken immune system can protect against Campylobacter colonisation. CjaA is a transporter of amino-acids and we have identified several other similar transporters, which are expressed in vivo, as candidates for vaccine. We will determine whether the targeting of these candidate proteins can be used as successful vaccine candidates. We will show conclusively whether any protection is antibody mediated by carrying out bursectomy studies. The identification of other vaccine targets will be important in the development of multivalent vaccines to over come potential problems of sero-type resistance. The protection achieved using the heterologously expressed CjaA was surprising. It is our belief that Salmonella may be acting as an adjuvant for the development of mucosal immunity to Campylobacter. We will determine whether the adjuvant like properties of the Salmonella are either passive or linked to a specific pathology. Using our understanding of intra-intestinal gene regulation of Campylobacter we will produce a Campylobacter whole cell killed vaccine (WCV), expressing the correct repertoire of surface proteins. We will then look at whether Salmonella works as adjuvant when used with this WCV. To determine the role of virulence traits on the efficacy of Salmonella Typhimurium we will study five strains as vectors for vaccines, wild-type (fully-virulent), SpaS (delayed-invasion), SsaU (reduced-intracellular-survival), fliM (reduced-inflammation in poultry), and aroAD (reduced-colonisation). We will assess the role of virulence in the development of the antibody response to heterologous proteins. We will identify the most efficacious and least efficacious strains and target investigations into the Th response to determine if there are specific differences, in reactions to different vaccine strains. A understanding of the driving force that leads to effective protection and clearance of this pathogen will allow us to make educated choices in the future development of vaccine adjuvants for poultry. Joint with BB/D000866/1.