A modular synthetic route to size-defined immunogenicHaemophilus influenzaeb antigens is key to the identification of an octasaccharide lead vaccine candidate
Abstract:A Haemophilus influenzae b vaccine lead antigen was identified by the immunological evaluation of chemically precisely defined capsular polysaccharide repeating unit oligosaccharides.
“…1b). Immunogenicity studies of the synthesized conjugates 2–5 on Zika rabbit model revealed that tetrameric conjugate 2 is the sufficient epitope for the new synthetic glycoconjugate Hib vaccine [42]. Fig.…”
Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.
“…1b). Immunogenicity studies of the synthesized conjugates 2–5 on Zika rabbit model revealed that tetrameric conjugate 2 is the sufficient epitope for the new synthetic glycoconjugate Hib vaccine [42]. Fig.…”
Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.
“…Early work on polysaccharides produced a series of three‐dimensional structures derived from X‐ray diffraction of fibers. The conformation in solution, crucial to understand the biological functions of polysaccharides, remained elusive due to lack of proper analytical techniques. The high structural diversity results from the different monosaccharide units (e.g., glucose, galactose, mannose) which can be substituted with multiple functional groups (e.g., acetyl, amine, sulfate).…”
In analogy to polypeptides and polynucleotides, polysaccharides tend to form helical secondary structures, as well as higher hierarchical assemblies. Nevertheless, the conformation of polysaccharides in solution remains in most cases elusive due to their intrinsic complexity and lack of analytical techniques. In this review, we discuss the different helical shapes adopted by polysaccharides, with particular focus on how the helical character is exploited to form supramolecular assemblies, such as inclusion complexes with linear guest molecules and co‐helices with polynucleotide strands. Several methodologies are used to tune the polysaccharides conformation, ranging from ion‐mediated coil‐helix transition to chemical synthesis of well‐defined compounds with specific modifications. The latter provides ideal tailor‐made probes for structural studies, with the aim to correlate their three‐dimensional structure and the macroscopic properties. Applications of oligosaccharides with defined shapes in molecular recognition and catalysis are envisioned.
“…A similar length‐dependent immunological activity was observed for the Haemophilus influenzae b antigens . Chemically synthesized glycoconjugates containing oligoribosyl‐ribitol‐phosphate (PRP) with 4 to 10 repeating units show different immunogenicities, with the tetramer and octamer able to elicit the highest antibody levels.…”
The conformation of am olecule strongly affects its function, as demonstrated for peptides and nucleic acids. This correlation is much less establishedf or carbohydrates, the most abundant organic materials in nature. Recent advances in synthetic and analytical techniques have enabled the study of carbohydrates at the molecular level. Recurrent structural features were identified as responsible for particular biological activities or materialp roperties. In this Minireview,r ecent achievements in the structuralc haracterization of carbohydrates, enabled by systematic studies of chemically defined oligosaccharides, are discussed. These findings can guide the development of more potent glycomimetics. Synthetic carbohydrate materials by design can be envisioned.
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