Delivery of protein antigens and DNA by virulence-attenuated strains of Salmonella typhimurium and Listeria monocytogenes

J Biotechnol. 2000 Sep 29;83(1-2):19-26. doi: 10.1016/s0168-1656(00)00293-5.

Abstract

Two different plasmid-vector systems were developed which allow the efficient production and presentation of protein antigens in antigen-presenting cells (APC) by means of virulence-attenuated bacteria. The first antigen-delivery system is based on the secretion machinery of the Escherichia coli hemolysin (HlyA-type I secretion system), which transports proteins, possessing the specific HlyA secretion signal (HlyA(s)) at the C-terminus, across both membranes of gram-negative bacteria. This system functions in all gram-negative bacteria that possess the TolC-analogous protein in the outer membrane. This outer membrane protein is necessary for the stable anchoring of the type I secretion apparatus in the cell envelope. Suitable HlyA(s)-fused antigens are secreted with high efficiency by E. coli and by virulence-attenuated strains of Salmonella, Shigella, Vibrio cholerae and Yersinia enterocolitica. The other vector system expresses the heterologous antigen under the control of an eukaryotic promoter in a similar fashion as in plasmids commonly used for vaccination with naked DNA. This plasmid DNA is introduced into APCs with the help of virulence-attenuated self-destructing Listeria monocytogenes mutants. After synthesis of the heterologous protein, epitopes of the antigen are presented by the APC together with MHC class I molecules. This system functions in macrophages and dendritic cells in vitro and can also be used in a modified form in animal models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / administration & dosage*
  • Escherichia coli / genetics
  • Hemolysin Proteins / administration & dosage
  • Listeria monocytogenes / genetics*
  • Listeria monocytogenes / metabolism
  • Listeria monocytogenes / pathogenicity
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity
  • Vaccines, Attenuated / administration & dosage*
  • Vaccines, DNA / administration & dosage*

Substances

  • Antigens, Bacterial
  • Hemolysin Proteins
  • Vaccines, Attenuated
  • Vaccines, DNA