To Develop Vaccination Approaches to the Control of Campylobacter in Poultry

Campylobacter jejuni remains the leading cause of bacterial enteritis in the UK, with over 40,000 cases reported in England and Wales in 2004. Furthermore a large-scale study for the Food Standards Agency estimated that in the community up to eight times as many cases may go unreported. Although the routes and sources of infections are not fully understood, the handling and/or consumption of contaminated poultry meat are believed to be risk factors. In Britain and elsewhere a large number of the poultry flocks, both intensively farmed and free-range/organic, are heavily colonised by the organism. However, it appears to cause no harm to the avian host. Biosecurity can go some where to reducing the incidence in poultry, but it is considered opinion that supplementary measure(s) are also necessary. Vaccination is one such measure.
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Previous Defra-funded work at VLA has shown that a Campylobacter vaccine may be feasible. Significant protection was obtained using an oral, sub-unit vaccine and particularly by a live vaccine and a DNA vaccine. We propose to continue this research in order to understand the basis of the observed protection and to use this information in the development of more effective vaccines that would be of use to the poultry industry and, in turn, to the consumer.
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DNA vaccination is a fairly recent approach in the fight against disease, but there is now considerable research in the area. In fact, the first two DNA vaccines for veterinary medicine have been licensed this year. Following the success with this approach in the previous DEFRA project VLA filed a patent application for a C. jejuni DNA vaccine for poultry. Therefore, our first objective in this proposal is to optimise the DNA vaccination model and to determine the underlying mechanisms that lead to protection. The experimental vaccine is some way off being a licensed product, but the model represents a 'gold standard' for further vaccination work. We intend to study the effects of varying the vaccination levels, and challenge doses and times on the efficacy. An array of accompanying immunological studies will be done in order to understand protection. This will greatly assist in the further development of vaccines.
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The second objective is to develop an improved, more economically realistic DNA vaccination protocol. The DNA vaccine developed previously contains the gene of a single C. jejuni antigen (flagellin). We intend to produce vaccines using the genes of other antigens, either singly or in combination, and to test these in challenge studies. The most effective of these will then be used for further studies. Realistically, broiler vaccination would involve administering the vaccine either directly into the egg ('in ovo') or orally. The efficacy of the vaccine will be tested in experimental models employing both of these routes, either singly or in combination. The vaccine will be incorporated into a delivery system developed at CSL, York. In addition, the genes encoding avian immunmodulatory molecules will be added to the vaccine in order to enhance the appropriate protective responses.
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The third objective is to develop alternative vaccines. If a DNA vaccine is not feasible, more established vaccination strategies may be effective. Previous live vaccine studies at VLA showed good protection. To develop this further a number of mutant C. jejuni strains will be tested for their ability to colonise birds for a short period only, so that they persist long enough to induce a protective response but have been cleared by the age of slaughter. Potential vaccine strains will then be tested in a chick model.
Similarly, an oral, sub-unit vaccine consisting of potentially protective antigens administered in the micro-encapsulation delvery system developed at CSL will be investigated.
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The fourth objective will look at the potential for maternal immunisation to help in the control of campylobacters. There is evidence that anti-C. jejuni antibodies derived from infected breeding birds afford some protection against colonisation in the first 2-3 weeks of a chick's life. If antibody levels could be boosted by maternal immunisation, this may provide additional protection, epsecially if successfully combined with in ovo or chick vaccination. To this end, we intend to establish breeding flocks at VLA that will be immunised with vaccines developed in objectives 2 and 3. We will then immunise some of their eggs/chicks, and others will be untreated, and their susceptibility to infection will be determined.
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The final objective will be to collate all results and to present a written report of findings and recommendations to Defra.
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It is hoped this work will lead to an effective vaccine(s) to control C. jejuni in poultry, which could be taken forward by industry for commercial development. A successful vaccine would have obvious benefits for the tax-payer/consumers and the farmers, as a safer food product would be beneficial to all.