Protein-conjugated synthetic di- and trisaccharides of pneumococcal type 17F exhibit a different immunogenicity and antigenicity than tetrasaccharide

Velasco, Elsa; Verheul, A. F. M.; Veeneman, G. H.; Gomes, Luiz Fernando; Boom, Jacques H. van; Verhoef, J.; Snippe, H.

doi:10.1016/0264-410x(93)90172-t

Cited by 35 publications

(23 citation statements)

References 24 publications

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“…The saccharides were coupled via the 3-aminopropyl spacer to carrier protein KLH in a stepwise reaction: the amino-terminal groups of the OS fragment and KLH were activated by S acetylation and Br acetylation, respectively, and coupled via a thioether linkage (2). The conjugates were purified over a Sepharose CL-6B column and dialyzed against phosphate-buffered saline.…”

Section: Chemicalsmentioning

confidence: 99%

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Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice

et al. 2001

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The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri-and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.

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Section: Chemicalsmentioning

confidence: 99%

“…Pn 14 and 17F PS were purified as described previously (2,32). Sera, diluted to an absorbance of 0.5, were incubated overnight at 4°C with different amounts of PS 6A, 6B, 14, and 17F as inhibitors.…”

Section: Chemicalsmentioning

confidence: 99%

Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice

et al. 2001

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Section: Pneumococcal Synthetic Oligosaccharide-based Vaccinesmentioning

confidence: 99%

“…Meanwhile we and other groups have been working on improving the immunogenicity of neoglycoconjugates against different S. pneumoniae serotypes in animal models: Di-, tri-, and tetrasaccharides related to polysaccharide type 17F conjugated to keyhole limpet hemocyanin (KLH) protein [69,70] and tri-and tetrasaccharides related to type 23 conjugated to KLH protein [71]; Di-, tri-, and tetrasaccharides related to type 6B conjugated to KLH protein [72]; Di-, tri-, and tetrasaccharide related to type 3 conjugated to the crossreactive material of diphteria toxin (CRM197) protein [60] and most recently overlapping oligosaccharide varying from tri-to dodecasaccharides related to polysaccharide type 14 conjugated to CRM197 protein [73,74].…”

Section: Pneumococcal Synthetic Oligosaccharide-based Vaccinesmentioning

confidence: 99%

“…Immunization of mice with synthetic hexasaccharide of glycosylphosphatidylinositol malarial toxin conjugated to a protein carrier was reported to protect the mice from an otherwise lethal dose of malaria parasites [67]. A fully synthetic carbohydrate-based antitumor candidate vaccine for the common T-synthase was recently reported [68].Meanwhile we and other groups have been working on improving the immunogenicity of neoglycoconjugates against different S. pneumoniae serotypes in animal models: Di-, tri-, and tetrasaccharides related to polysaccharide type 17F conjugated to keyhole limpet hemocyanin (KLH) protein [69,70] and tri-and tetrasaccharides related to type 23 …”

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The Future of Synthetic Carbohydrate Vaccines: Immunological Studies on Streptococcus pneumoniae Type 14

Safari¹,

Rijkers²,

Snippe³

2012

The Complex World of Polysaccharides

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Additional information is available at the end of the chapter http://dx.doi.org/10.5772/48326 IntroductionStudies on synthetic carbohydrates to be used as potential vaccine candidates for polysaccharide encapsulated bacteria were started in the mid-1970s. They were the logical follow-up to studies being performed at that time on the immunogenicity of antigens composed of carrier proteins and synthetic hapten groups. Hapten-carrier complexes were first introduced in immunology by Karl Landsteiner in the early 1900s [1]. He discovered that (i) small organic molecules with a simple structure, such as phenyl arsonates and nitrophenyls, do not provoke antibodies by themselves, but (ii) if those molecules are attached covalently, by simple chemical reactions, to a protein carrier, then antibodies against those small organic molecules are evoked. Since their introduction, these haptencarrier complexes have become excellent tools to elucidate the role of different antigenreactive cells in the immune response [2]. The key players in this immunological process are thymus-derived T cells and bone marrow-derived B cells. The former group of lymphoid cells is responsible for various phenomena of cell-mediated immunity, e.g. delayed hypersensitivity, allograft-, and graft-versus-host reactions, and reacts with specific determinants on the carrier protein (T cell epitopes). The latter group of lymphoid cells (B cells) give rise to the precursors of antibody-secreting cells, and reacts with both the carrier protein and the synthetic haptenic determinants. This results in antibody formation to both the carrier and the hapten.The reason to apply the above concepts and techniques to carbohydrate antigens was to address an immunological problem: polysaccharide molecules are classified as so-called thymus-independent (TI) antigens, because they do not require T cells to induce an immune response of B cells. As a result, the antibodies formed are mainly of the IgM class and have aThe Complex World of Polysaccharides 618 low avidity. Moreover, no immunological memory is generated and the antigens are poorly immunogenic in infants. Latter characteristic has major implications for development of vaccines against polysaccharide encapsulated bacteria. It was hypothesized that by linking small carbohydrates (oligosaccharides) to a carrier protein, the immunogenic behavior would change to that of a thymus-dependent (TD) antigen. Therefore, the studies of both Goebel [3,4] and Campbell and Pappenheimer [5], who first isolated the antigenic determinant of Streptococcus pneumoniae type 3, were combined and extended. The hapteninhibition studies by Mage and Kabat [6] demonstrated that the antibody-combining site of type 3 pneumococcal polysaccharide consists of two to three cellobiuronic acid units. In the dextran-anti-dextran system extensively studied by Kabat and colleagues [7] the upper size limit of the antibody-combining site appeared to be a hexa-or heptasaccharide and the lower limit was estimated to be somewhat larger than a monosac...

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Preparation of Glycoconjugate Vaccines

Zou

Jennings

2008

Carbohydrate‐Based Vaccines and Immunotherapies

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Protein-conjugated synthetic di- and trisaccharides of pneumococcal type 17F exhibit a different immunogenicity and antigenicity than tetrasaccharide

Cited by 35 publications

References 24 publications

Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice

Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice

The Future of Synthetic Carbohydrate Vaccines: Immunological Studies on Streptococcus pneumoniae Type 14

Preparation of Glycoconjugate Vaccines

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