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Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1.

Authors
  • Fontaine, A
  • Arondel, J
  • Sansonetti, P J
Type
Published Article
Journal
Research in Microbiology
Publisher
Elsevier
Publication Date
Jan 01, 1990
Volume
141
Issue
7-8
Pages
907–912
Identifiers
PMID: 2101481
Source
Medline
License
Unknown

Abstract

Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.

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