Fimbriae of enterotoxigenic Escherichia coli function as a mucosal carrier for a coupled heterologous antigen.
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.
Verdonck
F
F
Laboratory of Veterinary Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. Frank.Verdonck@UGent.be
De Hauwere
V
V
Bouckaert
J
J
Goddeeris
B M
BM
Cox
E
E
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002772:Cholera Toxin / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D008213:Lymphocyte Activation; D012709:Serum Albumin / Q000276:immunology*; D013552:Swine
D000907:Antibodies, Bacterial; D007071:Immunoglobulin A, Secretory; D012709:Serum Albumin; D002772:Cholera Toxin