Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein

Group B Streptococcus is a pathogen that chiefly infects immunocompromised individuals and neonates. To combat this infection, at-risk mothers are currently given antibiotics before birth to prevent exposure of neonates to the bacteria. A vaccine would be beneficial, as it would allow mothers to com...

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Main Author: MacCalman, Thomas
Format: Thesis (University of Nottingham only)
Language:English
Published: 2023
Subjects:
Online Access:https://eprints.nottingham.ac.uk/73790/
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author MacCalman, Thomas
author_facet MacCalman, Thomas
author_sort MacCalman, Thomas
building Nottingham Research Data Repository
collection Online Access
description Group B Streptococcus is a pathogen that chiefly infects immunocompromised individuals and neonates. To combat this infection, at-risk mothers are currently given antibiotics before birth to prevent exposure of neonates to the bacteria. A vaccine would be beneficial, as it would allow mothers to combat this infection without excessive use of antibiotics. As encapsulated bacteria, the main structure available as a target antigen is the polysaccharide capsule itself, rather than any underlying structures. For this reason, glycoconjugate vaccines are being synthesised which use surface polysaccharides conjugated to carrier proteins to improve their immunogenicity. This project studies the stability of candidate polysaccharides for use in a glycoconjugate vaccine. The polysaccharides were provided by GSK vaccines, who requested the use of specific hydrodynamic methodology. The polysaccharides were found to be generally stable, only seeing small changes in hydrodynamic properties after exposure to stress, but in many cases it is likely that the differences seen are due to minor experimental variation rather than genuine structural differences. The polysaccharides were also tested for possible association effects with blood plasma proteins: serum albumin, fibrinogen and immunoglobulin. The polysaccharides were again found to be stable in the presence of these molecules. Together, these results suggest that these molecules are suitable for further testing and development to generate a vaccine.
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spelling nottingham-737902025-02-28T15:18:15Z https://eprints.nottingham.ac.uk/73790/ Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein MacCalman, Thomas Group B Streptococcus is a pathogen that chiefly infects immunocompromised individuals and neonates. To combat this infection, at-risk mothers are currently given antibiotics before birth to prevent exposure of neonates to the bacteria. A vaccine would be beneficial, as it would allow mothers to combat this infection without excessive use of antibiotics. As encapsulated bacteria, the main structure available as a target antigen is the polysaccharide capsule itself, rather than any underlying structures. For this reason, glycoconjugate vaccines are being synthesised which use surface polysaccharides conjugated to carrier proteins to improve their immunogenicity. This project studies the stability of candidate polysaccharides for use in a glycoconjugate vaccine. The polysaccharides were provided by GSK vaccines, who requested the use of specific hydrodynamic methodology. The polysaccharides were found to be generally stable, only seeing small changes in hydrodynamic properties after exposure to stress, but in many cases it is likely that the differences seen are due to minor experimental variation rather than genuine structural differences. The polysaccharides were also tested for possible association effects with blood plasma proteins: serum albumin, fibrinogen and immunoglobulin. The polysaccharides were again found to be stable in the presence of these molecules. Together, these results suggest that these molecules are suitable for further testing and development to generate a vaccine. 2023-07-22 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/73790/1/Thomas%20MacCalman%20Thesis.pdf MacCalman, Thomas (2023) Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein. PhD thesis, University of Nottingham. pathogens Streptococcus glycoconjugates vaccines
spellingShingle pathogens
Streptococcus
glycoconjugates
vaccines
MacCalman, Thomas
Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title_full Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title_fullStr Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title_full_unstemmed Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title_short Hydrodynamics and stability of Group B Streptococcus polysaccharides and CRM197 protein
title_sort hydrodynamics and stability of group b streptococcus polysaccharides and crm197 protein
topic pathogens
Streptococcus
glycoconjugates
vaccines
url https://eprints.nottingham.ac.uk/73790/