PMID: 2101481Sep 1, 1990Paper

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

Research in Microbiology
A FontaineP J Sansonetti

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.

References

May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M L BernardiniP J Sansonetti
Apr 1, 1988·Vaccine·A A LindbergF P Reinholt
Sep 1, 1988·Gut·D ClementsR N Allan
Jan 1, 1988·Annual Review of Microbiology·A T Maurelli, P J Sansonetti
Apr 1, 1987·Zentralblatt Für Bakteriologie, Mikrobiologie, Und Hygiene. Series A, Medical Microbiology, Infectious Diseases, Virology, Parasitology·S B BalodaT Wadström
Dec 1, 1985·The Journal of Infectious Diseases·W E Farrar
Apr 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·M BelfortF Maley

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Citations

May 1, 1995·Research in Immunology·P Dubois, L Pereira da Silva
Jun 1, 1994·Current Opinion in Biotechnology·J J Mekalanos
Jan 1, 1994·International Journal of Technology Assessment in Health Care·J J Mekalanos
May 11, 2006·Epidemiology and Infection·K A TalukderD A Sack
May 16, 2002·Infection and Immunity·Malabi M VenkatesanJoan Butterton
Dec 22, 2006·Expert Review of Vaccines·Malabi M Venkatesan, Ryan T Ranallo
Jun 22, 1999·Infection and Immunity·T S CosterT L Hale
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·T SamandariM B Sztein
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshihiko SuzukiChihiro Sasakawa
Jun 14, 2019·Cellular Microbiology·Eileen M Barry, Myron M Levine

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