Identification of the Smallest Structure Capable of Evoking Opsonophagocytic Antibodies against
            <i>Streptococcus pneumoniae</i>
            Type 14

Safari, Dodi; Dekker, Huberta A. T.; Joosten, John; Michalik, Dirk; Souza, Adriana Carvalho de; Adamo, Roberto; Lahmann, Martina; Sundgren, Andreas; Oscarson, Stefan; Kamerling, Johannis P.; Snippe, H.

doi:10.1128/iai.00472-08

Cited by 100 publications

(113 citation statements)

References 35 publications

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“…We found that the fragments with a linear and/or incomplete branched structure did not elicit specific antibodies against native Pn14PS (Fig. 4: JJ118, JJ42, JJ141, DM65, JJ153, JJ9, JJ6 and DM35) [73]. High titer of anti-Pn14PS IgG antibodies was observed when the complete branched structure fragments, conjugated to the protein carrier were used in the mouse model (Fig.…”

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confidence: 87%

“…Antibody titers were expressed as the log10 of the dilution Filled circle = glucose (Glc); open circle = galactose (Gal), and filled square = N-acetylglucosamine (GlcNAc). In conclusion, the present study has shown that the branched trisaccharide Glc-(Gal-)GlcNAc is the core structure inducing Pn14PS-specific antibodies and that the neighboring galactose at the non-reducing end significantly contributes to the induction of phagocytosispromoting antibodies [73]. Our study provides evidence that the branched tetrasaccharide Gal-Glc-(Gal-)GlcNAc is a prime candidate for a synthetic oligosaccharide conjugate vaccine against infections caused by S. pneumoniae type 14 [73].…”

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confidence: 89%

“…We continued to investigate further how small the minimal structure in Pn14PS can be and still produce specific antibodies against native polysaccharide type 14 [73]. 16 overlapping oligosaccharide fragments of Pn14PS were synthesized as described previously [76][77][78][79] and were conjugated to the protein carrier CRM197.…”

Section: Identification Of the Minimal Structure Of Oligosaccharide Cmentioning

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%

“…We found that the sera containing antibodies against Pn14PS were also capable of promoting the phagocytosis of S. pneumoniae type 14. Conjugates that did not evoke specific antibodies against polysaccharide type 14 also did not display phagocytic capacity [73]. …”

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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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mentioning

confidence: 87%

mentioning

confidence: 89%

Section: Identification Of the Minimal Structure Of Oligosaccharide Cmentioning

confidence: 99%

Section: Pneumococcal Synthetic Oligosaccharide-based Vaccinesmentioning

confidence: 99%

mentioning

confidence: 99%

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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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Antigens: CarbohydratesII

Kieber-Emmons

Monzavi‐Karbassi

Kieber‐Emmons

2020

Encyclopedia of Life Sciences

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Glycosylation is critical for a wide range of biological processes across both normal and disease states. Carbohydrate antigens, for example, are polymeric chains of diverse monomeric sugar molecules that play a fundamental role in the pathogenicity and virulence of many organisms. Moreover, these pathogen‐associated glycan structures can also be found in association with other types of cells, including tumours. These types of glycan commonalities have helped generate critical discoveries in terms of glycan structure, allowing for the development of working hypotheses for their functions, in addition to the development of agents that target or mediate their expression levels. Therefore, through discussion of glycans as antigens, new insights of key molecular and cellular interactions between them and immune cells can be discerned, and the implication of these interactions in health and disease is enhanced. Numerous reviews and even this ELS series have described the structure of carbohydrates and glycans in general. Key Concepts Glycosylation is the most abundant post‐translational modification of proteins. Glycans expand the chemical diversity of the genetic code. Antigens are a collection of epitopes that affects recognition by the immune system. Antigens and immunogens are very different. Molecular mimicry of glycans profoundly affects the pathophysiology of infection and neoplasia. Lectin‐family receptors and antibodies have been used to define carbohydrate antigens. Clustering of epitopes defines glycan antigens better than nonclustered epitopes. Carbohydrate antigens can define danger signals to the immune system through pattern recognition receptors. Clustering associates with different B‐cell populations for processing as immunogens. MHC and T‐cell receptors see atoms in particular arrays, not as a single molecular species – hence cross‐reactivity with zwitterionic carbohydrate structures. While carbohydrate‐based vaccines have been developed, as cancer vaccines they are not as effective. Metabolism is the next frontier to understanding glycan expression patterns.

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