Open AccessPartially Assembled K99 Fimbriae Are Required for Protection
Author(s) -
Miguel Ascon,
Javier OchoaRepáraz,
Nancy Walters,
David W. Pascual
Publication year - 2005
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.73.11.7274-7280.2005
Subject(s) - fimbria , enterotoxigenic escherichia coli , biology , microbiology and biotechnology , protein subunit , epitope , antibody , immunity , heterologous , pilus , bacterial outer membrane , enterobacteriaceae , fimbriae proteins , escherichia coli , virology , immune system , gene , immunology , genetics , enterotoxin
Antibodies to K99 fimbriae afford protection to F5+ bovine enterotoxigenicEscherichia coli (ETEC). Previous studies show that murine dams immunized withSalmonella vaccine vectors stably expressing K99 fimbriae confer protection to ETEC-challenged neonatal pups. To begin to address adaptation of the K99 scaffold to display heterologous B- and T-cell epitopes, studies were conducted to determine how much of the assembled K99 fimbria is required to maintain protective immunity. Sequential deletions in the K99 gene clusters were made, resulting in diminished localization of the K99 fimbrial subunit in the outer membrane. As placement of the K99 fimbrial subunit became progressively contained within the vaccine vector, diminished immunoglobulin A (IgA) and IgG1 antibody titers, as well as diminished Th2-type cytokine responses, were observed in orally immunized mice. Deletion offanGH , which greatly reduced the export of the fimbrial subunit to the outer membrane, showed only partial reduction in protective immunity. By contrast, deletion offanDEFGH , which also reduced the export of the fimbrial subunit to the outer membrane but retained more subunit in the cytoplasm, resulted in protective immunity being dramatically reduced. Thus, these studies showed that retention of K99 fimbrial subunit as native fimbriae or with the deletion offanGH is sufficient to confer protection.