Abstract
Antibodies against the cell surface carbohydrates of many microbial pathogens protect against infection, which led to the first generation of carbohydrate vaccines based on purified bacterial polysaccharides. These polysaccharide vaccines are rapidly becoming replaced by the more immunogenic glycoconjugate vaccines in which the cell surface carbohydrate is covalently attached to an appropriate carrier protein. Compared to the corresponding polysaccharide vaccines, glycoconjugate vaccines are diverse and structurally complex, which comprise polysaccharide or oligosaccharide fragments, linked through a variety of coupling chemistries to different carrier proteins. As for polysaccharide vaccines, the potency of glycoconjugate vaccines cannot be reliably predicted by biological assays, and therefore their development, quality control, and licensure rely mostly on the physicochemical characterization of the starting polysaccharide and protein, activated or derivatized intermediates and the conjugate vaccine produced. Glycoconjugate vaccines against Haemophilus influenzae type b and selected serogroups/types of Neisseria meningitidis and Streptococcus pneumoniae have been licensed and strategies for their manufacturing, testing, and regulation established. These principles are being applied to develop conjugate vaccines against additional strains of these bacteria and other pathogens including Streptococcus, Salmonella, Staphylococcus, Escherichia coli, Klebsiella, Enterococcus, Shigella, Vibrio, as well as pathogenic fungi such as Candida albicans and Cryptococcus neoformans. These challenges are being met by the development of new conjugation strategies combined with improved analytical techniques and new approaches to making well-defined conjugates using synthetic and biosynthetic methods.
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Acknowledgments
One of us (NR) would like to thank PATH and all the vaccine manufacturers who have made available samples of polysaccharides and glycoconjugate vaccines and for the many fruitful discussions, as well as the assistance of students Kirstin Anderson, Taigh Anderson, and Carey Pike with checking the manuscript and references.
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Ravenscroft, N., Costantino, P., Talaga, P., Rodriguez, R., Egan, W. (2015). Glycoconjugate Vaccines. In: Nunnally, B., Turula, V., Sitrin, R. (eds) Vaccine Analysis: Strategies, Principles, and Control. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45024-6_8
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