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

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 elic...

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Veröffentlicht in:Research in microbiology 1990-09, Vol.141 (7-8), p.907-912
Hauptverfasser: Fontaine, A., Arondel, J., Sansonetti, P.J.
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container_issue 7-8
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container_title Research in microbiology
container_volume 141
creator Fontaine, A.
Arondel, J.
Sansonetti, P.J.
description 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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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. 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source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Animals
Bacterial Vaccines - genetics
Bacterial Vaccines - isolation & purification
Bacteriology
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Humans
Macaca
Microbiology
Mutation
Shigella dysenteriae - genetics
Shigella dysenteriae - immunology
Shigella flexneri - genetics
Shigella flexneri - immunology
Shigella, Vaccine, Shigellosis
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, Attenuated - genetics
Vaccines, Attenuated - isolation & purification
Vaccines, Synthetic - genetics
Vaccines, Synthetic - isolation & purification
Virulence - genetics
Virulence, Mutations
title Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1
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