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This research will investigate whether phase variation influences the observed resistance of campylobacter jejuni to vaccines by studying the impact of phase variation on campylobacter colonisation and avoidance of host immune responses using four approaches.
<ul><li>The frequency and nature of phase variation events occurring during in-vitro growth of campylobacter will be assessed, and modelling used to determine whether non-selective bottlenecks account for changes observed during chicken colonisation experiments.</li>
<li>The impact of adaptive immune responses to natural colonisation on phase variation of campylobacter genes will be measured. Immune evasion will be assessed by investigating whether the immune responses associated with long-term colonisation impact on phase variation. Immune responses generated by a natural infection will be investigated for their impact on colonisation or selection of phase variants. Models will be used to determine whether observed changes in the proportions of phase variation are due to the drift associated with high phase variation rates, to non-selective bottlenecks or to selection of these variants.</li>
<li>The impact of phase variation on protection by or avoidance of immune responses to whole-cell or sub-unit vaccines will be examined by testing the hypothesis that campylobacter can escape vaccine-induced immune responses by phase variation of target antigens. Using vaccinated and non-vaccinated birds, a global view of the role of phase variants will be obtained by examining the impact of whole-cell vaccine-induced immune responses on a selection of phase variants. To test whether phase variation of a single gene mediates immune evasion, further work will examine the impact of immune responses induced by sub-unit vaccines.</li>
<li>The impact of phase variation rates on the protection by, or avoidance of, immune responses to vaccines will be examined. Phase locked-ON mutants of specific genes in vaccinated and non-vaccinated birds will be used to investigate whether the loss of ability to undergo phase variation prevents immune evasion.</li></ul>
<p>Overall, these objectives will significantly inform and further our knowledge of the functions of phase variation of campylobacter jejuni infections and are of relevance across the bacterial world where phase variation plays diverse and significant role in commensal and pathogenic behaviour. </p>
<p>Background: The control of campylobacter in poultry is predicted to significantly reduce human cases of infection, with vaccination being one of the routes used to achieve this. Current campylobacter vaccines have a variable efficacy in preventing colonisation in chickens. One reason given is that campylobacter induces the production of antibodies against its surface components. However these antibodies do not prevent colonisation or clear the bacteria from birds. It is suggested that this is achieved by campylobacter switching off the expression of key surface molecules, so that they are not recognised by the chicken's antibodies, a process known as phase variation.</p>
<p>This research will investigate the effect of phase variation and its interplay with the immune responses of the host. This will be achieved by testing the hypothesis that the induction and evasion of host immunity is correlated with phase-variable changes in surface structures of campylobacter. If true, it may be possible to improve the efficacy of campylobacter vaccines if the protective processes associated with phase variation are by-passed. </p>