| Summary: | <i>Campylobacter</i> infections in humans are traced mainly to poultry products. While vaccinating poultry against <i>Campylobacter</i> could reduce the incidence of human infections, no vaccine is yet available on the market. In our previous study using a plasmid DNA prime/recombinant protein boost vaccine regimen, vaccine candidate YP437 induced partial protective immune responses against <i>Campylobacter</i> in broilers. In order to optimise vaccine efficacy, the vaccination protocol was modified using a protein prime/protein boost regimen with a different number of boosters. Broilers were given two or four intramuscular protein vaccinations (with the YP437 vaccine antigen) before an oral challenge by <i>C. jejuni</i> during a 42-day trial. The caecal <i>Campylobacter</i> load, specific systemic and mucosal antibody levels and caecal microbiota in the vaccinated groups were compared with their respective placebo groups and a challenge group (<i>Campylobacter</i> infection only). Specific humoral immune responses were induced, but no reduction in <i>Campylobacter</i> caecal load was observed in any of the groups (<i>p</i> > 0.05). Microbiota beta diversity analysis revealed that the bacterial composition of the groups was significantly different (<i>p</i> ≤ 0.001), but that vaccination did not alter the relative abundance of the main bacterial taxa residing in the caeca. The candidate vaccine was ineffective in inducing a humoral immune response and therefore did not provide protection against <i>Campylobacter</i> spp. infection in broilers. More studies are required to find new candidates.
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