Dissection of Protective Responses to Heterologous Campylobacter Vaccines

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. <P>
We will determine whether the targeting of these candidate proteins can be used as successful vaccine candidates. We will show conclusively that any protection is antibody mediated by carrying out bursectomy studies. <P>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 is 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. <P>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). <P>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.<P> 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/D00019X/1