Safety and immunogenicity of a prototype oral whole-cell killed Campylobacter vaccine administered with a mucosal adjuvant in non-human primates.

The safety and immunogenicity of two prototype oral Campylobacter killed whole-cell (CWC) vaccines were tested in rhesus monkeys. Animals were immunized with a primary two-dose series (days 0 and 14) of vaccine consisting of CWC (10(10) particles/dose) given alone or in combination with 0.5-1000 micrograms of the heat-labile enterotoxin of Escherichia coli as an oral adjuvant (OA). A booster vaccination, 4 weeks after primary immunization, was given to animals receiving CWC alone or supplemented with 0.5, 5 or 50 micrograms of OA. Both CWC and CWC-OA were well tolerated, with no adverse side-effects noted. Campylobacter-specific as well as adjuvant-specific antibody-secreting cells (ASCs) were determined in peripheral blood collected 7 days after each vaccine dose. Campylobacter-specific IgA ASC responses were enhanced by OA in a dose-dependent manner (p = 0.025), while IgG ASC responses were not. Seroconversions (both IgA and IgG) to Campylobacter antigens were also enhanced in monkeys receiving adjuvanted vaccine. No significant booster vaccination effect was observed in circulating ASCs in any of the immunization groups. In vitro T-cell proliferative responses to Campylobacter jejuni antigens were somewhat enhanced in both the CWC and CWC-OA immunization groups. These results demonstrate that CWC-OA is safe and superior to CWC alone in its ability to stimulate both local and systemic Campylobacter-specific IgA and IgG responses in primates and they support its further evaluation in human clinical studies.