FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.1.2

Title of the proposal

Synthesis and Immunological Properties of Conjugates Containing Detoxified Bacterial Lipopolysaccharides bound to Immuno-modulant b-D-Glucan

Institute

Slovak Academy of Sciences, Laboratory of Microbial Polymers, Institute of Chemistry
Dubravska cesta 9, 842 38 Bratislava, Slovak Republic

Contact

Research subject for a potential FP6 project

The objective of this proposal is to prepare a semi-synthetic three-component conjugate vaccine against Vibrio cholerae 01 by linking a detoxified cholera lipopolysaccharide (LPS) through a yeast glucan matrix to a protein carrier. Such a vaccine should be suitable for routine vaccination including young children. Enhancement of the serum IgG response specific to the LPS of V.cholerae 01 will be gained by devising a sandwich-type conjugate vaccine. The O-specific polysaccharide of V. cholerae (OSP) is relatively small which limits its immunogenicity even as a conjugate. In the proposed vaccine constructs, the OSP chains will be covalently linked to a suitable matrix to form a comb-like structure with high density of OSP molecules. Multiplication of the antigen molecules in such construct should result in its enhanced immunogenicity. Yeast cell-wall b-glucan with immunomodulating properties, isolated and appropriately derivatized at the Institute of Chemistry, is the matrix of choice. We assume that besides serving as a matrix for the bound O-antigens, b-glucan will contribute to increased immunogenicity due to its adjuvant properties.
The Laboratory of Microbial Polymers has been involved for several decades in isolation of micro-bial polysaccharides, their characterization and modification, as well as in study of biological properties of the obtained derivatives. Its research team can contribute with its skills in isolation and chemical derivatization of the carbohydrate materials.

Recent international cooperation of the research team

Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia; Department of Surgery, J.H. Quillen School of Medicine, East Tennessee State University, Johnson City, TN, USA; Laboratory of Genetics, Department of Morphology, National School of Biological Sciences, Mexico City, Mexico

Proposer´s relevant publications related to the research subject

1. J. Sanudla, G. Kogan, M. Kacurakova, and E. Machova : Microbial (1->3)-b-glucans, their preparation, physico-chemical characterization and immunomodulatory activity. Carbohydr. Polym. 38 (1999) 247-253.
2. S. Bystricky, E. Machova, A. Malovikova, and G. Kogan: Determination of the cross-linking effect of adipic acid dihydrazide on glycoconjugate preparation. Glycocon. J. 16 (1999) 691-695.
3 S. Bystricky, S.C. Szu, J. Zhang, and P. Kovac: Conformational differences among mono- and oligosaccharide fragments of the O-specific polysaccharides of Vibrio cholerae 01 revealed by circular dichroism. Carbohydr. Res. 314 (1998) 135-139.
4. D. Pavliakova, C. Chu, S. Bystricky, N.W. Tolson, J. Shiloach, J.B. Kaufman, D.A. Bryla, J.B. Robbins, and R. Schneerson: Treatment with succinic anhydride improves the immunogenicity of Shigella flexneri type 2a O- specific polysaccharide-protein conjugates in mice. Infect. Immun. 67 (1999) 5526-5529.