STOPENTERICS · Vaccination against Shigella and ETEC: novel antigens, novel approaches

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.