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Meeds, Oliver (2023) A review of glycoconjugate vaccines: The current state of the technology, considerations for the future, and the gold standard carrier protein, CRM(197). MRes thesis, University of Nottingham.

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Abstract

Part A:

Conjugation of bacterial capsular polysaccharides to immunogenic carrier proteins has been employed for almost five decades to protect infants and adults against bacterial infections. This review investigates the immune mechanisms, conjugation chemistry, and carrier protein interactions that define glycoconjugate technology, and reports on the recent developments that have facilitated a renewed interest into the field of conjugated vaccines. With novel methodologies such as bioconjugation and Generalized Modules for Membrane Antigens (GMMA) reaching maturity, and the carrier protein CRM(197) seeing a research-renaissance, molecular characterization has never been more important. Elucidation of the physiochemical properties of prospective therapeutics is a crucial quality control measure that allows their structural integrity, stability, and immunogenicity to be verified. Thus, a special mention is made to the hydrodynamic methods that ensure current and novel therapeutics remain safe and efficacious.

Part B:

Conjugation of thymus independent polysaccharide antigens to immunogenic carrier proteins improves their immunogenicity and confers long lasting immunity. This approach has been employed for decades to protect global populations against bacterial infections. With the omnipresent threat of antibiotic resistance growing ever greater, glycoconjugate technology has seen a resurgence as a strategy to prevent lesser-researched bacterial infections before antibiotic treatment is required. Despite recent advances, the genetically detoxified diphtheria toxin CRM197 remains the gold standard carrier protein and has also been investigated as a carrier of cancer antigens. As glycoconjugate technology experiences a research-renaissance an added pressure is placed on manufacturers to produce high quality therapeutic constituents. Improving the knowledge of molecular characteristics of vaccine components is therefore a crucial cog in the developmental machine. In this current work, we report on the high inherent stability of CRM197 under appropriate storage conditions but highlight an unusual tendency to aggregate under forces like those exerted on the protein during manufacturing or transportation. Further comment is made regarding the influence of polysaccharide serotype on therapeutic hydrodynamics, emphasizing the importance of structural considerations in vaccine design.

Item Type:	Thesis (University of Nottingham only) (MRes)
Supervisors:	Harding, Stephen E
Keywords:	glycoconjugates, vaccines, immunology, antigens, polysaccharides
Subjects:	Q Science > QP Physiology > QP501 Animal biochemistry Q Science > QR Microbiology > QR180 Immunology
Faculties/Schools:	UK Campuses > Faculty of Science > School of Biosciences
Item ID:	76028
Depositing User:	HARDING, Prof Stephen
Date Deposited:	13 Dec 2023 14:49
Last Modified:	13 Dec 2023 14:49
URI:	https://eprints.nottingham.ac.uk/id/eprint/76028

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