Shigella dysenteriae

Live Attenuated Enteric Pathogen Vaccines: Shigella dysenteriae type 1

Shigella dysentery is the cause of nearly a million deaths annually in children under 5 years, in resource poor settings. Shigella dysenteriae type 1 causes the most virulent form of the infection, and is responsible mainly for explosive epidemics in refugee camps and in times of natural or man-made disaster. It therefore affects the most vulnerable and powerless members of the world community. A vaccine is urgently required, and live attenuated bacteria offer the most affordable likely solution.

Phase 1

A study coordinated by Prof David Lewis (Principal Investigator) and Dr Christine Sadorge, Pasteur Institute, Paris, of immune responses of healthy human volunteers to a live attenuated Shigella dysenteriae type 1 vaccine commenced in the Institute in October 2003 completed in April 2004. This was the first occasion this novel live attenuated Sh. dysenteriae type 1 vaccine developed by Prof. Philippe Sansonetti, Institute Pasteur, Paris has been investigated in humans. This was also the first study to use the Contained Use Regulations to run a human Phase 1 vaccine trial, requiring completely novel practices and procedures, and making full use of the Institute's unique isolation facilities.

Phase 2a

The Institute was subsequently awarded a grant of over £250,000 to conduct a Phase 2a trial of this vaccine at St George's which completed in 2006. It recruited over 100 persons (half in London, Principal Investigator Prof David Lewis and half in Paris) into a safety and efficacy trial of the new vaccine in two dose levels, compared with placebo. The study was run under the Contained Use Regulations but as an outpatient trial. This regulatory process has been possible due to the very high levels of biological containment afforded by this attenuated strain. Recruitment is now closed and the results have been published.

Publications

• A dose-escalation Phase 1 clinical trial of immunogenicity and reactogenicity of live attenuated Shigella dysenteriaei icsA- toxA- ent- fep-:HgR vaccine in healthy adults. Christine Sadorge, Philippe J. Sansonetti, Nathalie Beveridge, Schale Frazer, Rafaela Giemza, Julie Johnson, Helen Liddy, Catherine A. Cosgrove, P. Allavena, George E. Griffin, David J.M. Lewis Vaccine 2008; 26: 978—987.
• Safety and Immunogenicity of SC599, an Oral Live Attenuated Shigella dysenteriae type-1 Vaccine in Healthy Volunteers: Results of a Phase 2, Randomized, Double-Blind Placebo-Controlled Trial. O Launay, C Sadorge, N Jolly, B Poirier, S Bechet, D van der Vliet, V Seffer, N Fenner, K Dowling, R Giemza, J Johnson, A Ndiaye, M Vray, P Sansonetti, P Morand, C Poyart, D Lewis, M-L Gougeon. Vaccine 2009; 27: 1184Ð1191