The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Markus W Weishaupt - One of the best experts on this subject based on the ideXlab platform.
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a semi synthetic oligosaccharide conjugate vaccine candidate confers protection against streptococcus pneumoniae serotype 3 infection
Chemistry & Biology, 2016Co-Authors: Sharavathi Guddehalli Parameswarappa, Katrin Reppe, Andreas Geissner, Petra Menova, Subramanian Govindan, Adam D J Calow, Annette Wahlbrink, Markus W WeishauptAbstract:The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic Glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.
Emilia Cappelletti - One of the best experts on this subject based on the ideXlab platform.
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development of a glycoconjugate vaccine to prevent meningitis in africa caused by meningococcal serogroup x
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Francesca Micoli, Simona Rondini, Maria Rosaria Romano, Marta Tontini, Emilia Cappelletti, Massimiliano Gavini, Daniela Proietti, Erwin Swennen, Laura Santini, Sara FilippiniAbstract:Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in the African meningitis belt, and has a high associated mortality. The meningococcal serogroups A, W, and X have been responsible for epidemics and almost all cases of meningococcal meningitis in the meningitis belt over the past 12 y. Currently no vaccine is available against meningococcal X (MenX). Because the development of a new vaccine through to licensure takes many years, this leaves Africa vulnerable to new epidemics of MenX meningitis at a time when the epidemiology of meningococcal meningitis on the continent is changing rapidly, following the recent introduction of a glycoconjugate vaccine against serogroup A. Here, we report the development of candidate glycoconjugate vaccines against MenX and preclinical data from their use in animal studies. Following optimization of growth conditions of our seed MenX strain for polysaccharide (PS) production, a scalable purification process was developed yielding high amounts of pure MenX PS. Different Glycoconjugates were synthesized by coupling MenX oligosaccharides of varying chain length to CRM197 as carrier protein. Analytical methods were developed for in-process control and determination of purity and consistency of the vaccines. All conjugates induced high anti-MenX PS IgG titers in mice. Antibodies were strongly bactericidal against African MenX isolates. These findings support the further development of glycoconjugate vaccines against MenX and their assessment in clinical trials to produce a vaccine against the one cause of epidemic meningococcal meningitis that currently cannot be prevented by available vaccines.
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evaluation of a group a streptococcus synthetic oligosaccharide as vaccine candidate
Vaccine, 2010Co-Authors: Anna Kabanova, Francesco Berti, Maria Rosaria Romano, Daniela Proietti, Erwin Swennen, Immaculada Margarit, Guido Grandi, Giuliano Bensi, Emiliano Chiarot, Emilia CappellettiAbstract:Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of Glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing.
Andreas Geissner - One of the best experts on this subject based on the ideXlab platform.
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a semi synthetic oligosaccharide conjugate vaccine candidate confers protection against streptococcus pneumoniae serotype 3 infection
Chemistry & Biology, 2016Co-Authors: Sharavathi Guddehalli Parameswarappa, Katrin Reppe, Andreas Geissner, Petra Menova, Subramanian Govindan, Adam D J Calow, Annette Wahlbrink, Markus W WeishauptAbstract:The identification of immunogenic glycotopes that render glycoconjugate vaccines protective is key to improving vaccine efficacy. Synthetic oligosaccharides are an attractive alternative to the heterogeneous preparations of purified polysaccharides that most marketed glycoconjugate vaccines are based on. To investigate the potency of semi-synthetic Glycoconjugates, we chose the least-efficient serotype in the current pneumococcal conjugate vaccine Prevnar 13, Streptococcus pneumoniae serotype 3 (ST3). Glycan arrays containing synthetic ST3 repeating unit oligosaccharides were used to screen a human reference serum for antibodies and to define the recognition site of two ST3-specific protective monoclonal antibodies. The glycan array screens identified a tetrasaccharide that was selected for in-depth immunological evaluation. The tetrasaccharide-CRM197 carrier protein conjugate elicited protective immunity as evidenced by opsonophagocytosis assays and protection against pneumonia caused by ST3 in mice. Formulation of the defined protective lead candidate glycotope has to be further evaluated to elicit optimal long-term immunity.
Barbara Imperiali - One of the best experts on this subject based on the ideXlab platform.
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chemoenzymatic synthesis and applications of prokaryote specific udp sugars
Methods in Enzymology, 2017Co-Authors: Cristina Y Zamora, Nathaniel S Schocker, Michelle M Chang, Barbara ImperialiAbstract:Abstract This method describes the chemoenzymatic synthesis of several nucleotide sugars, which are essential substrates in the biosynthesis of prokaryotic N - and O -linked glycoproteins. Protein glycosylation is now known to be widespread in prokaryotes and proceeds via sequential action of several enzymes, utilizing both common and modified prokaryote-specific sugar nucleotides. The latter, which include UDP-hexoses such as UDP-diNAc-bacillosamine (UDP-diNAcBac), UDP-diNAcAlt, and UDP-2,3-diNAcManA, are also important components of other bacterial and archaeal Glycoconjugates. The ready availability of these “high-value” intermediates will enable courses of study into inhibitor screening, glycoconjugate biosynthesis pathway discovery, and unnatural carbohydrate incorporation toward metabolic engineering.
Kerry L Wilkinson - One of the best experts on this subject based on the ideXlab platform.
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quantitative analysis of glycoconjugate precursors of guaiacol in smoke affected grapes using liquid chromatography tandem mass spectrometry based stable isotope dilution analysis
Food Chemistry, 2011Co-Authors: Kerry A Dungey, Yoji Hayasaka, Kerry L WilkinsonAbstract:Abstract Guaiacol has been shown to accumulate in glycoconjugate forms in the fruit and leaves of grapevines following vineyard exposure to bushfire smoke. To investigate the glycosylation of guaiacol in smoke-affected grapes, a quantitative stable isotope dilution analysis method using liquid chromatography-tandem mass spectrometry was developed and validated, using the [2H4]-labelled analogue of guaiacol β- d -glucopyranoside as internal standard. The method was subsequently applied to the analysis of grapes sampled from grapevines exposed to either bushfire or experimental smoke, enabling compositional comparisons of guaiacol Glycoconjugates in smoke-affected grapes from different varieties to be determined, for the first time. Guaiacol glucose–pentose disaccharide conjugates (i.e. glucosides with a terminal pentose) were found to be the most abundant glycoconjugate precursors present in smoke-affected grapes, regardless of grape variety or smoke source. Higher concentrations of Glycoconjugates were measured in extracts of whole berry homogenate than juice.