Induction of Th1 polarized immune responses by thiolated Eudragit-coated F4 and F18 fimbriae of enterotoxigenic Escherichia coli

Eur J Pharm Biopharm. 2011 Oct;79(2):226-31. doi: 10.1016/j.ejpb.2011.04.016. Epub 2011 May 6.

Abstract

Diarrhea in newborn and weaned piglets is mainly induced by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4 (K88) and F18 (F107). In this study, we evaluated F4 and F18 coated with thiolated Eudragit microspheres (TEMS) as a candidate for an oral vaccine. The average particle sizes of TEMS, F4-loaded TEMS, and F18-loaded TEMS were measured as 4.2±0.75 μm, 4.7±0.50 μm, and 4.5±0.37 μm, respectively. F4 is more efficiently encapsulated than F18 in the loading with TEMS. In the release test, F4 and F18 fimbriae were protected in acidic circumstances, whereas most were released at pH 7.4 of intestine circumstances. Production of TNF-α and NO from RAW 264.7 cells was increased in a time-dependent manner after exposure to all groups, whereas only F4- or F18-loaded TEMS-stimulated IL-6 secretion. The levels of IFN-γ from mouse splenocytes after exposure to F4 or F18 were increased while IL-4 was not detectable. These results suggest that F4- and F18-loaded TEMS may effectively induce immune response with the efficient release of antigens to appropriate target sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / chemistry
  • Bacterial Vaccines / immunology*
  • Cell Line
  • Enterotoxigenic Escherichia coli / immunology*
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / prevention & control
  • Female
  • Fimbriae Proteins / immunology*
  • Fimbriae, Bacterial / immunology*
  • Interleukin-4 / immunology
  • Interleukin-6 / immunology
  • Intestinal Mucosa / immunology
  • Mice
  • Mice, Inbred ICR
  • Microspheres
  • Nitric Oxide / immunology
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / pharmacology*
  • Th1 Cells / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Vaccines
  • Interleukin-6
  • Polymethacrylic Acids
  • Tumor Necrosis Factor-alpha
  • Fimbriae Proteins
  • Interleukin-4
  • methylmethacrylate-methacrylic acid copolymer
  • Nitric Oxide