SAFETY AND IMMUNOGENICITY OF A PROTOTYPE ORAL WHOLE-CELL KILLED CAMPYLOBACTER VACCINE ADMINISTERED WITH A MUCOSAL ADJUVANT IN NONHUMAN-PRIMATES

The safety and immunogenicity of two prototype oral Campylobacter kill ed whole-cell (CWC) vaccines were tested in rhesus monkeys. Animals we re immunized with a primary two-dose ser ies (days 0 and 14) of vaccin e consisting of CWC (10(10) particles/dose) given alone or in combinat ion with 0.5-1000 mu g of the heat-labile enterotoxin of Escherichia c oli as an oral adjuvant (OA). A booster vaccination, 4 weeks after pri mary immunization, was given to animals receiving CWC alone or supplem ented with 0.5, 5 or 50 mu g of OA. Both CWC and CWC-OA were well tole rated with no adverse side-effects noted Campylobacter-specific as wel l as adjuvant-specific antibody-secreting cells (ASCs) were determined in peripheral blood collected 7 days after each vaccine dose. Campylo bacter-specific IgA ASC responses were enhanced by OA in a dose-depend ent manner (p = 0.025), while IgG ASC responses were not. Seroconversi ons (both IgA and IgG) to Campylobacter antigens were also enhanced in monkeys receiving adjuvanted vaccine, No significant booster vaccinat ion effect was observed in circulating ASCs in any of the immunization groups. In vitro T-cell proliferative responses to Campylobacter jeju ni antigens were somewhat enhanced in both the CWC and CWC-OA immuniza tion groups. These results demonstrate that CWC-OA is safe and superio r to CWC alone in its ability to stimulate both local and systemic Cam pylobacter-specific IgA and IgG responses in primates and they support its further evaluation in human clinical studies.