Hitri, K. and Kuttel, M. and De Benedetto, G. I. and Lockyer, K. and Gao, F. and Hansal, P. and Rudd, T. R. and Beamish, E. and Rijpkema, S. and Ravenscroft, N. and Bolgiano, B. (2019) O-acetylation of typhoid capsular polysaccharide confers polysaccharide rigidity and immunodominance by masking additional epitopes., Vaccine, 37, 3866-3875, Elsevier.
Full text not available from this repository. (Use alternate locations listed below)Abstract
In this work, we explore the effects of O-acetylation on the physical and immunological characteristics of the WHO International Standards of Vi polysaccharide (Vi) from both Citrobacter freundii and Salmonella enterica serovar Typhi. We find that, although structurally identical according to NMR, the two Vi standards have differences with respect to susceptibility to de-O-acetylation and viscosity in water. Vi standards from both species have equivalent mass and O-acetylation-dependent binding to a mouse monoclonal antibody and to anti-Vi polyclonal antisera, including the WHO International Standard for human anti-typhoid capsular Vi PS IgG. This study also confirms that human anti-Vi sera binds to completely de-O-acetylated Vi. Molecular dynamics simulations provide conformational rationales for the known effect of de-O-acetylation both on the viscosity and antigenicity of the Vi, demonstrating that de-O-acetylation has a very marked effect on the conformation and dynamic behavior of the Vi, changing the capsular polysaccharide from a rigid helix into a more flexible coil, as well as enhancing the strong interaction of the polysaccharide with sodium ions. Partial de-O-acetylation of Vi revealed hidden epitopes that were recognized by human and sheep anti-Vi PS immune sera. These findings have significance for the manufacture and evaluation of Vi vaccines.
| Item Type: | Journal article (paginated) |
|---|---|
| Uncontrolled Keywords: | Enteric Glycoconjugate Molecular modelling Nuclear magnetic resonance Vaccine Vi polysaccharide |
| Subjects: | Applied computing > Life and medical sciences Computing methodologies > Modeling and simulation |
| Date Deposited: | 23 Sep 2019 |
| Last Modified: | 10 Oct 2019 15:31 |
| URI: | http://pubs.cs.uct.ac.za/id/eprint/1341 |
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