Description of Invention: Shigellosis, an inflammatory enteric infection is on the World Health Organization's priority list of disease to be prevented. It can be prevented by O-specific polysaccharide (O-SP)-protein conjugate vaccines in adults. But the highest incidence and severity of S. sonnei shigellosis is in young children and the O-SP-protein conjugate that was effective in adults cannot overcome the age-related immunogenicity of vaccines in this age group. Thus, a better immunogen is needed.
The immunogen claimed in this application uses O-SP formed by isolation of low molecular mass of O-SP- core fragments from the native product that allows a conjugate to be formed with a "sun" configuration as opposed to "lattice" type conjugates made previously, based on a synthetic saccharide conjugate of S. dysenteriae type 1 that induced significantly higher antibody levels than the "lattice" type conjugate. IgG antibody levels induced in young outbred mice with the "sun" configuration S. sonnei conjugate were higher than conjugates made with the full length O-SP.
This application claims the vaccine compositions described above, methods of making the vaccine compositions of the technology, and methods of preventing and/or treating Shigellosis.
Applications: Development of Shigella sonnei vaccines and diagnostics.
Advantages: Known regulatory path for conjugate vaccines, potential reduction in number of doses of vaccine, pediatric vaccine.
Development Status: Vaccine candidates have been synthesized and preclinical studies have been performed.
Inventors: John B Robbins (NICHD) Rachel Schneerson (NICHD) Joanna Kubler-kielb (NICHD) Christopher P Mocca (NICHD)
J Kubler-Kielb et al. The elucidation of the structure of the core part of the LPS from Plesiomonas shigelloides serotype O17 expressing O-polysaccharide chain identical to the Shigella sonnei O-chain. Carbohydr Res. 2008 Dec 8;343(18):3123-3127. [ PubMed abs ]
JB Robbins et al. Shigella sonnei O-specific oligosaccharide-core-protein conjugates: synthesis, characterization and immunogenicity in mice. Proc Natl Acad Sci. 2009; doi 10.1073/pnas.0900891106.
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