Anderson, Taigh and Jiang, Hao and Ní Cheallaigh, Aisling and Bengtsson, Dennis and Oscarson, Stefan and Cairns, Chantelle and St. Michael, Frank and Cox, Andrew and Kuttel, Michelle M. (2024) Formation and immunological evaluation of Moraxella catarrhalis glycoconjugates based on synthetic oligosaccharides, Carbohydrate Polymers, 332, 121928, Elsevier.
Full text not available from this repository. (Use alternate locations listed below)Abstract
Published work has shown that glycoconjugate vaccines, based on truncated detoxified lipopolysaccharides from Moraxella catarrhalis attached through their reducing end to a carrier protein, gave good protection for all three serotypes A, B, and C in mice immunisation experiments. The (from the non-reducing end) truncated LPS structures were obtained from bacterial glycosyl transferase knock-out mutants and contained the de-esterified Lipid A, two Kdo residues and five glucose moieties. This work describes the chemical synthesis of the same outer Moraxella LPS structures, spacer-equipped and further truncated from the reducing end, i.e., without the Lipid A part and containing four or five glucose moieties or four glucose moieties and one Kdo residue, and their subsequent conjugation to a carrier protein via a five‑carbon bifunctional spacer to form glycoconjugates. Immunisation experiments both in mice and rabbits of these gave a good antibody response, being 2–7 times that of pre-immune sera. However, the sera produced only recognized the immunizing glycan immunogens and failed to bind to native LPS or whole bacterial cells. Comparative molecular modelling of three alternative antigens shows that an additional (2 → 4)-linked Kdo residue, not present in the synthetic structures, has a significant impact on the shape and volume of the molecule, with implications for antigen binding and cross-reactivity.
| Item Type: | Journal article (paginated) |
|---|---|
| Subjects: | Computing methodologies > Modeling and simulation > Simulation types and techniques > Molecular simulation |
| Date Deposited: | 08 Aug 2024 08:38 |
| Last Modified: | 08 Aug 2024 08:39 |
| URI: | https://pubs.cs.uct.ac.za/id/eprint/1673 |
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