Determinants of the immunogenicity of live virulent and mutant Vibrio cholerae O1 in rabbit intestine

Abstract

Determinants of the capacity of live Vibrio cholerae 01 isolates to evoke specific immune responses in intestinal mucosa were studied in rabbits, using mucosal immunoglobulin A (IgA) antitoxin as the measured immune response. Antitoxin responses were evoked mostly by the primary inoculation and were dose dependent; secondary-type responses were modest and occurred only when the booster inoculum was large, i.e., 1010 CFU. The efficiency of mucosal immunization correlated closely with the mucosal colonizing capacity of the infecting strain and was otherwise independent of toxin genotype (A' B' or A-B') or whether the strain was motile or nonmotile. Live bacteria evoked mucosal antitoxin more efficiently than did purified cholera toxin. Prior immunization with a nontoxinogenic (A-B-) V. chokrae strain interfered significantly with the induction of mucosal antitoxin by subsequent immunization with its fully toxinogenic (A' B') parent. These results demonstrate the marked efficiency with which live V. cholerae stimulate a specific enteric mucosal secretory IgA response. They support the view that mucosal colonization aids efficient delivery of bacterial antigens to responsive subepithelial lymphoid tissue. This might occur by transfer of colonizing bacteria through M cells into Peyer patches or by efficient delivery of secreted toxin to M cells by mucosa-associated organisms. Preexisting antibacterial immunity interferes with colonization, which may prevent efficient antigenic stimulation and which may explain the relatively weak response to booster immunization. The same process may also limit the efficacy of hybrid enteric bacterial vaccines when there is preexisting mucosal immunity to the carrier organism due to either natural exposure or prior immunization with another vaccine that uses the same carrier.

Combined parenteral and oral immunization results in an enhanced mucosal immunoglobulin A response to Shigella flexneri

“…The first significant increase in the IgA antishigella LPS activity over preimmunization values was found on day 6, with the response peaking on day 8. These findings are similar to those we have previously reported concerning the response following single immunization with live invasive or even noninvasive shigellae (26,30). No IgG antishigella LPS activity was found in the intestinal secretions (Fig.…”

Colonization of the oral cavity of mice by an unidentified streptococcus

“…Its ability to stimulate both responses could be explained by its capacity to colonize the intestinal epithel-ium (unpublished preliminary results). It has been demonstrated that live microorganisms that colonize intestinal mucosa provide a more effective stimulus for an immune response than killed bacteria and purified antigens that can be degraded by the gastric barrier (25). Adherence of live bacteria to the ilial mucosa facilitates uptake by the Peyer's patches, which are a major IgA induction site of the common mucosal immune system and can also be the site of an IgG response (6).…”

Vibrio cholerae O1 adherence to villi and lymphoid follicle epithelium: in vitro model using formalin-treated human small intestine and correlation between adherence and cell-associated hemagglutinin levels

“…Recently accumulated knowledge has suggested that mucosal colonization with V. cholerae 01 is important for development of local immunity against cholera. Studies in animal model systems have supported the view that colonization aids efficient delivery of V. cholerae 01 antigens to responsive subepithelial lymphoid tissue (24,25). Volunteer studies have pointed out the importance of local anticolonization antibodies (18).…”