title: The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization.
abstract: Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.
authors.affiliation: Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium. Frank.Verdonck@ablynx.com
authors.forename: Frank
authors.initials: F
authors.lastname: Verdonck
authors.forename: Jussi Joonas
authors.initials: JJ
authors.lastname: Joensuu
authors.forename: Edith
authors.initials: E
authors.lastname: Stuyven
authors.forename: Julie
authors.initials: J
authors.lastname: De Meyer
authors.forename: Mikko
authors.initials: M
authors.lastname: Muilu
authors.forename: Minna
authors.initials: M
authors.lastname: Pirhonen
authors.forename: Bruno Maria
authors.initials: BM
authors.lastname: Goddeeris
authors.forename: Jan
authors.initials: J
authors.lastname: Mast
authors.forename: Viola
authors.initials: V
authors.lastname: Niklander-Teeri
authors.forename: Eric
authors.initials: E
authors.lastname: Cox