STOPENTERICS

"Vaccination against Shigella and ETEC: novel antigens, novel approaches"

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'To contribute to the development of vaccines against Shigella and ETEC for children of the developing world, STOPENTERICS will provide novel solutions by imposing a two-fold paradigm switch: (i) to break the dogma of serotype-specificity by inducing a cross-protective immunity (ii) to improve the immunogenicity of Shigella glycoconjugates by using synthetic oligosacharides mimicking the lipopolysaccharide O-antigen. The possibilities offered by genomics/proteomics and bacterial outer membrane blebs (OMB) will be exploited to identify virulence proteins conserved throughout Shigella or ETEC isolates. For ETEC, the development of a safe, immunogenic ST (heat stable) toxoid is a priority. State-of-the-art glycochemistry and sugar-protein carrier conjugation will allow engineering optimal Shigella glycoconjugates with focus on the five most prevalent serotypes. The ultimate aim is to optimize chances for the best coverage by combining cross-protective and serotype-specific antigens, thus ensuring the development of efficient multivalent vaccines that will help reduce the burden of diarrheal diseases. At all stages of the R & D process, candidate antigens will be considered in light of immunomonitoring data obtained in naturally-infected individuals, and volunteers undergoing vaccine trials. Regarding the latter, Phase-1 clinical trials with two vaccine candidates are planned as proofs–of-concept of (i) a synthetic oligosaccharides approach mimicking Shigella O-antigens, and (ii) a Shigella OMB-based vaccines to be tested after validation of preclinical studies. STOPENTERICS is a unique combination of laboratories, platforms, vaccinology centres from academia and industry in the North and the South, integrated to successfully develop new vaccines, from R&D toward clinical trials. By promoting high-standard training capacity for young investigators, it will foster a new generation of researchers in neglected infectious diseases.'

Introduzione (Teaser)

Leading scientists across the world have joined forces to engineer novel vaccines against Shigella and Escherichia coli. From antigen discovery to evaluation, to vaccine development and clinical trials, the STOPENTERICS project envisions inducing effective, cross-protective immunity.

Descrizione progetto (Article)

Infections with Shigella and E. coli are common among infants and children below the age of five in the developing world. However, to date there is no vaccine against these pathogens with significant protective capacity for these age groups.

The main aim of the EU-funded 'Vaccination against Shigella and ETEC: Novel antigens, novel approaches' (STOPENTERICS) project will be to resolve this issue. Project members will develop novel vaccine candidates against shigella and enterotoxigenic E. coli (ETEC) for children. The consortium partners are particularly interested in inducing cross-protective immunity and improving the immunogenicity of shigella glycoconjugates by using synthetic oligosaccharides.

To this end, scientists aim to use colonic infection animal models to test combinations of cross-protective protein antigens and the most prevalent synthetic oligosaccharides. A number of parameters that includes route of immunisation and the associated adjuvant will be optimised to elicit strong T cell responses and B/T cell memory. An important line of work entails the identification of novel correlates of protection and markers for immunomonitoring infected patients and volunteers enrolled in clinical trials.

Additionally, the consortium partners are exploring shigella and shigella-derived outer membrane proteins (GMMA) as sources for the discovery and evaluation of novel cross-protective antigens. Synthetic oligosaccharides mimic the serotype-specific determinants carried by the shigella 'O-Antigen'-one of the most prevalent shigella serotypes. When combined to form shigella semi-synthetic glycoconjugates for use in protein vaccines, immunogenicity could be improved.

With respect to ETEC antigens, the consortium has discovered a great heterogeneity among the genomes of various E. coli isolates. Bioinformatics analysis is currently being performed to identify a common set of ETEC-specific genes, preferentially encoding putative surface-exposed proteins.

Candidate antigens are being produced, purified and evaluated for their capacity to confer protection in pre-clinical models. A vaccine containing a synthetic oligosaccharide and a GMMA-based vaccine are ready to be tested in clinical trials.