| Summary: | <i>Campylobacter jejuni</i> is the leading bacterial cause of human gastroenteritis worldwide and the handling or consumption of contaminated poultry meat is the key source of infection. <i>C. jejuni</i> proteins FlpA and SodB and glycoconjugates containing the <i>C. jejuni N</i>-glycan have been separately reported to be partially protective vaccines in chickens. In this study, two novel glycoproteins generated by protein glycan coupling technology—G-FlpA and G-SodB (with two and three <i>N</i>-glycosylation sites, respectively)—were evaluated for efficacy against intestinal colonisation of chickens by <i>C. jejuni</i> strain M1 relative to their unglycosylated variants. Two independent trials of the same design were performed with either a high challenge dose of 10<sup>7</sup> colony-forming units (CFU) or a minimum challenge dose of 10<sup>2</sup> CFU of <i>C. jejuni</i> M1. While antigen-specific serum IgY was detected in both trials, no reduction in caecal colonisation by <i>C. jejuni</i> M1 was observed and glycosylation of vaccine antigens had no effect on the outcome. Our data highlight inconsistencies in the outcome of <i>C. jejuni</i> vaccination trials that may reflect antigen-, challenge strain-, vaccine administration-, adjuvant- and chicken line-specific differences from previously published studies. Refinement of glycoconjugate vaccines by increasing glycosylation levels or using highly immunogenic protein carriers could improve their efficacy.
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