Author:

Keywords:

Administration, Oral, Animals, Antibodies, Bacterial, Cholera Toxin, Escherichia coli, Fimbriae, Bacterial, Immunity, Mucosal, Immunization, Immunoglobulin A, Secretory, Lymphocyte Activation, Serum Albumin, Swine, Science & Technology, Physical Sciences, Life Sciences & Biomedicine, Chemistry, Multidisciplinary, Pharmacology & Pharmacy, Chemistry, F4 (K88) fimbriae, mucosal carrier, enterotoxigenic Escherichia coli, cholera toxin, pig, TOXIN-B-SUBUNIT, CHOLERA-TOXIN, IMMUNE-RESPONSES, ORAL IMMUNIZATION, DRUG-DELIVERY, F4 FIMBRIAE, PURIFIED F4, PIGS, K88, ADJUVANT, 0903 Biomedical Engineering, 0904 Chemical Engineering, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences, 4003 Biomedical engineering

Abstract:

Receptor-mediated uptake of orally administered antigen can lead to an antigen-specific immune response, whereas oral administration of most other non-replicating soluble antigens results in the induction of oral tolerance. In the present study, it is shown that fimbriae purified from an F4(K88)(+) enterotoxigenic Escherichia coli strain can function as a mucosal carrier molecule for the model antigen human serum albumin (HSA). Glutaraldehyde-coupled F4/HSA conjugates were able to bind F4 receptor positive (F4R(+)) enterocytes, but not to F4R(-) enterocytes. Moreover, oral immunization of F4R(+) pigs with F4/HSA conjugates induced a HSA-specific immune response, whereas oral immunization with HSA/HSA conjugates did not. This mucosal carrier function of F4 fimbriae was improved following oral co-administration of the F4/HSA conjugates with the mucosal adjuvant cholera toxin (CT) to F4R(+) pigs, since both humoral and cellular HSA-specific responses were significantly increased. In comparison with F4R(+) pigs, the HSA-specific response was reduced following oral F4/HSA+CT immunization of F4R(-) pigs. This indicates that F4 fimbriae as mucosal carrier and CT as adjuvant synergistically improve the induction of a HSA-specific immune response following oral immunization of pigs. These results could open new perspectives in the development of vaccines against enteropathogens.