Jonathan Dolan

CASE – Orthogonal ligation strategies for making well defined glycoconjugate vaccines

About me

Jonathan graduated with first class honours in chemistry (MChem) from Keele University in 2017. During his time at Keele, he completed a two final year projects entitled “Continuous Flow Iodination of Enaminones using a Dynamic Computer Controlled Liquid-Liquid Separation System” and “The Chemical Synthesis of GDP-α-D-ManUA from D-Mannose.” Jonathan moved to the University of Leeds in September 2017 to begin a PhD with Prof. Bruce Turnbull and Dr Mike Webb on developing Orthogonal ligation strategies for making well defined glycoconjugate vaccines supported by Iceni Diagnostics, Norwich in a BBSRC iCASE studentship award. Jonathans research interests focus on chemical modification of bacterial polysaccharides and utilising them to manipulate the immune system.

My project

Glycoconjugate vaccines for infectious diseases represent a strong emerging market, as evidenced by the recent GSK acquisition of Glycovaxyn and Novartis Vaccines. However, glycans generally make poor immunogens and glycoproteins/glycoconjugates are difficult to manufacture in the homogenous form necessary to pass regulatory scrutiny. In this project we aim to develop a toolbox of approaches for the preparation of glycoconjugate vaccines; with the ultimate aim to conjugate multiple different polysaccharide epitopes to specific sites on a protein scaffold (adjuvants) with low level of heterogeneity. Cholera toxin B-subunit (CTB) and polyomavirus (SV40) capsid have both been investigated as potential adjuvants in vaccine development and are well known within our group. Both have been investigated for the display of peptide and carbohydrate antigens, however have not been used for the display of an O-glycopeptide.

Multivalent glycoconjugate vaccine, where sortase A has been used to ligate antigen A, oxime ligation has been used to attach antigen B, CuAAC has been used to ligate antigen C and SPAAC has been used on antigen D.

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