STOPENTERICS

Bacterial diseases Projects

Vaccination against Shigella and ETEC: novel antigens, novel approaches

EC contribution: : € 11,460,630
Duration: : 60 months
Starting date: : 01/11/2010
Funding scheme: : Large scale project
Contract/Grant agreement number: : 261472
Project web-site: : http://stopenterics.bio-med.ch

Keywords: Shigella, ETEC, enteric infection, dysentery, vaccines, O-polysaccharides, synthetic sugars, conjugate vaccines, protein-based vaccines, immunomonitoring, experimental infection, experimental protection, clinical trials, training/e-learning

Summary:

STOPENTERICS aims at providing novel prophylactic solutions by imposing a two-fold paradigm switch in the development of vaccine candidates against Shigella and ETEC:

to break the dogma of serotype-specific protection and
to improve the immunogenicity of some already identified antigens.

In addition, since a set of new vaccine candidates corresponding to novel strategies have already reached an advanced stage, the consortium is in a position to achieve a proof of concept early on in the program. The program integrates basic research, particularly genomics, transcriptomics, proteomics, high-throughput technologies, and synthetic chemistry to identify novel antigens and generate new vaccine formulations, as well as immunology and development of cell-based and animal models to help rationalize R&D and prepare for transition to phase 1 trials. A particular effort will be dedicated, throughout the program, to immunomonitoring of natural Shigella and ETEC infections in order to generate and validate novel and reliable correlates of protection. Therefore, STOPENTERICS will adopt a pragmatic modus operandi illustrated by the strong momentum imposed to bring innovative candidates as quickly as possible through the R&D pipeline, including clinical trials carried out both in the North and in the South.
A particular strength of STOPENTERICS is its integration of a broad spectrum of expertise offered by a coalition of groups from Europe, Middle East, Asia and Africa in Shigella and ETEC biology, pathophysiology, immunology and vaccine testing. STOPENTERICS will also team up with two premier vaccine companies: Novartis, through the Novartis Vaccines Institute for Global Health, and Sanofi-Pasteur, both engaged in the consortium as scientific partners.
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Problem:

despite sustained efforts by a limited number of expert groups, there is not yet a vaccine against ETEC and Shigella, consequently these two pathovars continue to account for a large fraction of mortality and morbidity due to enteric infections.

Aim:

to develop a new paradigms of vaccination encompassing/integrating:

optimization of existing antigens (i.e. antigenization of ETEC ST toxin and synthesis of highly immunogenic Shigella O-polysaccharidic side chains),
discovery of novel protein antigens and outer membrand vesicles achieving serotype-independent cross protection, and
combination of such novel antigens with new adjuvants allowing production of high titers of protective antibodies and efficient T cell responses.

Expected Results:

To be able, by the end of the program, to carry out two "proof of concept" phase 1 trial (one synthetic polysaccharide conjugate and one outer membrane vesicle-based vaccines). To also develop novel biomarkers/assays for immunomonitoring, particularly correlates of protection in order to optimize the impact of clinical trials that will be carried out, based on the results obtained in the course of STOPENTERICS.

Potential applications:

Protection of the most exposed pediatric populations against cholera-like ETEC infection and bacillary dysentery.

Coordinator:

Philippe J. Sansonetti
Institut Pasteur
28 Rue du Docteur Roux
75724 Paris cedex 15
France
philippe.sansonetti@pasteur.fr

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