Improving live attenuated bacterial carriers for vaccination and therapy

  • Loessner H
  • Endmann A
  • Leschner S
 et al. 
  • 40

    Readers

    Mendeley users who have this article in their library.
  • 33

    Citations

    Citations of this article.

Abstract

Live attenuated bacteria are well established as vaccines. Thus, their use as carriers for prophylactic and therapeutic macromolecules is a logical consequence. Here we describe several experimental applications of bacteria to carry heterologous macromolecules into the murine host. First, Listeria monocytogenes are described that are able to transfer eukaryotic expression plasmids into host cells for gene therapy. High multiplicities of infection are still required for efficient gene transfer and we point out some of the bottlenecks that counteract a more efficient transfer and application in vivo. Then, we describe Salmonella enterica serovar Typhimurium (S. typhimurium) as an expression plasmid transfer vehicle for oral DNA vaccination of mice. We demonstrate that the stabilization of the plasmid transformants results in an improved immune response. Stabilization was achieved by replacing the origin of replication of the original high-copy-number plasmid by a low-copy-number origin. Finally, we describe Salmonella carriers for the improved expression of heterologous proteins. We introduce a system in which the plasmid is carried as a single copy during cultivation but is amplified several fold upon infection of the host. Using the same in vivo inducible promoter for both protein expression and plasmid amplification, a substantial increase in antigen expression in vivo can be achieved. A modification of this approach is the introduction of inducible gene expression in vivo with a low-molecular-weight compound. Using PBAD promoter and l-arabinose as inducer we were able to deliberately activate genes in the bacterial carrier. No background activity could be observed with PBAD such that an inducible suicide gene could be introduced. This is adding an important safety feature to such live attenuated carrier bacteria. © 2007 Elsevier GmbH. All rights reserved.

Author-supplied keywords

  • Amplifiable plasmids
  • Gene transfer
  • Inducible gene expression
  • Listeria monocytogenes
  • Salmonella typhimurium
  • Therapy
  • Vaccination

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Holger Loessner

  • Anne Endmann

  • Sara Leschner

  • Heike Bauer

  • Andrea Zelmer

  • Susanne zur Lage

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free