Abstract
The structures of the branched capsular polysaccharides of group B streptococcus type III (GBSIIIPS) and Streptococcus pneumoniae type 14 (Pn14PS) are identical apart from the (α2→3)-linked sialic acid in the side chains of GBSIIIPS. The present study tries to determine the minimal epitope in GBSIIIPS, using both a panel of anti-Pn14PS mouse sera and sera of humans vaccinated with either Pn14PS or GBSIIIPS. Type-specific Pn14PS antibodies that recognize the branched structure of Pn14PS have a low affinity for the native GBSIIIPS. Desialylation of GBSIIIPS results in dramatically higher affinity of anti-Pn14PS antibodies. Epitope specific anti-Pn14PS mouse antibodies and human sera of PCV7 vaccinees only recognized structures with the branching element -Glc-(Gal-)GlcNAc-, in particular -Gal-Glc-(Gal-)GlcNAc- in Pn14PS. On the other hand anti-GBSIIIPS human antibodies recognize predominantly the linear structure in the backbone of Pn14PS or GBSIIIPS, i.e., -Glc-GlcNAc-Gal-. This difference in antigenicity of Pn14PS and GBSIIIPS is in agreement with the difference in flexibility of the two polysaccharides caused by the presence or absence of sialic acid.
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References
Crumrine, M.H., Fischer, G.W., Balk, M.W.: Immunochemical cross-reactions between type III group B streptococcus and type 14 Streptococcus pneumoniae. Infect. Immun. 25(3), 960–963 (1979)
Gonzalez-Outeirino, J., Kadirvelraj, R., Woods, R.J.: Structural elucidation of type III group B streptococcus capsular polysaccharide using molecular dynamics simulations: the role of sialic acid. Carbohydr. Res. 340(5), 1007–1018 (2005)
Guttormsen, H.K., Baker, C.J., Nahm, M.H., Paoletti, L.C., Zughaier, S.M., Edwards, M.S., Kasper, D.L.: Type III group B streptococcal polysaccharide induces antibodies that cross-react with Streptococcus pneumoniae type 14. Infect. Immun. 70(4), 1724–1738 (2002)
Kadirvelraj, R., Gonzalez-Outeirino, J., Foley, B.L., Beckham, M.L., Jennings, H.J., Foote, S., Ford, M.G., Woods, R.J.: Understanding the bacterial polysaccharide antigenicity of streptococcus agalactiae versus streptococcus pneumoniae. Proc. Natl. Acad. Sci. U. S. A. 103(21), 8149–8154 (2006)
Weiman, S., Dahesh, S., Carlin, A.F., Varki, A., Nizet, V., Lewis, A.L.: Genetic and biochemical modulation of sialic acid O-acetylation on group B streptococcus: phenotypic and functional impact. Glycobiology 19(11), 1204–1213 (2009)
Mawas, F., Niggemann, J., Jones, C., Corbel, M.J., Kamerling, J.P., Vliegenthart, J.F.: Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic single repeating unit of type 14 pneumococcal polysaccharide coupled to CRM197. Infect. Immun. 70(9), 5107–5114 (2002)
Safari, D., Dekker, H.A., Joosten, J.A., Michalik, D., de Souza, A.C., Adamo, R., Lahmann, M., Sundgren, A., Oscarson, S., Kamerling, J.P., Snippe, H.: Identification of the smallest structure capable of evoking opsonophagocytic antibodies against Streptococcus pneumoniae type 14. Infect. Immun. 76(10), 4615–4623 (2008)
Kasper, D.L., Paoletti, L.C., Wessels, M.R., Guttormsen, H.K., Carey, V.J., Jennings, H.J., Baker, C.J.: Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J. Clin. Invest. 98(10), 2308–2314 (1996)
Zou, W., Mackenzie, R., Therien, L., Hirama, T., Yang, Q., Gidney, M.A., Jennings, H.J.: Conformational epitope of the type III group B streptococcus capsular polysaccharide. J. Immunol. 163(2), 820–825 (1999)
Jennings, H.J., Lugowski, C., Kasper, D.L.: Conformational aspects critical to the immunospecificity of the type III group B streptococcal polysaccharide. Biochemistry 20(16), 4511–4518 (1981)
Kasper, D.L., Baker, C.J., Baltimore, R.S., Crabb, J.H., Schiffman, G., Jennings, H.J.: Immunodeterminant specificity of human immunity to type III group B streptococcus. J. Exp. Med. 149(2), 327–339 (1979)
Wessels, M.R., Pozsgay, V., Kasper, D.L., Jennings, H.J.: Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J. Biol. Chem. 262(17), 8262–8267 (1987)
Acknowledgements
This study was supported by a grant from the European Commission under contract MRTN-CT-2004-005645. We thank Dr. Dennis Kasper, Channing laboratory, Harvard Medical School, Boston, MA, USA for the generous gift of purified polysaccharide of GBSIII, human anti-GBSIIIPS antibody, and a mouse monoclonal antibody against GBSIIIPS. We also thank Jovanka Besteboer, Alex Laarman and Ben de Jong (St. Antonious Hospital) for technical assistance.
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Safari, D., Dekker, H.A.T., Rijkers, G.T. et al. The immune response to group B streptococcus type III capsular polysaccharide is directed to the -Glc-GlcNAc-Gal- backbone epitope. Glycoconj J 28, 557–562 (2011). https://doi.org/10.1007/s10719-011-9354-1
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DOI: https://doi.org/10.1007/s10719-011-9354-1