We have previously shown that antibodies to cholera toxin (CT) reacted with the major outer membrane proteins (MOMPs) from Campylobacter jejuni on Western blot. Further, oral immunization with CT significantly protected against challenge with C. jejuni in an adult mouse intestinal colonization model. CT and heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli are related. LT and its double-mutant LT (R192G/L211A) (dmLT) are mucosal adjuvants. Unlike LT which is reactogenic, dmLT is safe for humans. In the current study, we determined whether rabbit anti-dmLT antibodies reacted with MOMPs from C. jejuni and whether immunization with dmLT would protect against C. jejuni. On Western blot, MOMPs from C. jejuni 48 (serotype O:19), C. jejuni 75 (O:3) and C. jejuni 111 (O:1,44) were probed with rabbit antibodies to dmLT. Adult BALB/c mice were orally immunized with dmLT and challenged with the above C. jejuni strains. Protection from colonization was studied by enumerating C. jejuni colonies in feces daily for 9 days. Serum antibody (IgG &IgA) and fecal antibody (IgA) responses to dmLT and C. jejuni MOMP were studied by ELISA. C. jejuni MOMPs did not react with antibodies to dmLT. Vaccination induced serum and stool antibody responses to dmLT and no antibody responses to C. jejuni MOMP in mice. Vaccinated mice showed reduced colonization and excretion of challenge bacteria compared to control mice. The differences in colonization were not statistically significant for strains 48 and 111, but significant for strain 75 on 2 of 9 days. The reduced excretion was not significant for strain 48, but significant for strains 111 and 75 for 2 and 3 days respectively out of 9 days. The protective efficacy of dmLT vaccine varied from 9.1% to 86.1%. The lack of cross-reaction between MOMPs and dmLT suggests that protection is not mediated by cross-reacting antibodies, but may be due to activation of innate immunity. dmLT could be incorporated into a C. jejuni vaccine to enhance vaccine efficacy.
Work supported by grant number MI03/13 from Kuwait University.