Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

Bazhenova, Aleksandra; Gao, Fang; Bolgiano, Barbara; Harding, Stephen E.

Abstract

The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and O-acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of Salmonella enterica subspecies enterica serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Salmonella Typhi and Shigella species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.

Citation

Bazhenova, A., Gao, F., Bolgiano, B., & Harding, S. E. (2021). Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis. Biophysical Reviews, 13(2), 221-246. https://doi.org/10.1007/s12551-021-00791-z

• Journal Article Type: Article
• Acceptance Date: Feb 25, 2021
• Online Publication Date: Apr 10, 2021
• Publication Date: Apr 1, 2021
• Deposit Date: Apr 9, 2021
• Publicly Available Date: Apr 9, 2021
• Journal: Biophysical Reviews
• Print ISSN: 1867-2450
• Electronic ISSN: 1867-2469
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 2
• Pages: 221-246
• DOI: https://doi.org/10.1007/s12551-021-00791-z
• Keywords: Biophysics; Molecular Biology; Structural Biology
• Public URL: https://nottingham-repository.worktribe.com/output/5437883
• Publisher URL: https://link.springer.com/article/10.1007/s12551-021-00791-z