Impact and Control of Sugar Size in Glycoconjugate Vaccines

Abstract

Glycoconjugate vaccines have contributed enormously to reducing and controlling encapsulated bacterial infections for over thirty years. Glycoconjugate vaccines are based on a carbohydrate antigen that is covalently linked to a carrier protein; this is necessary to cause T cell responses for optimal immunogenicity, and to protect young children. Many interdependent parameters affect the immunogenicity of glycoconjugate vaccines, including the size of the saccharide antigen. Here, we examine and discuss the impact of glycan chain length on the efficacy of glycoconjugate vaccines and report the methods employed to size polysaccharide antigens, while highlighting the underlying reaction mechanisms. A better understanding of the impact of key parameters on the immunogenicity of glycoconjugates is critical to developing a new generation of highly effective vaccines.

Elucidating the role of N-acetylglucosamine in Group A Carbohydrate for the development of an effective glycoconjugate vaccine against Group A Streptococcus

“…Over the last years, organic synthesis has been proposed for preparation of bacterial oligosaccharides, providing well defined structures easy to characterize, with absence of bacterial contaminants, and useful to correlate the immune response elicited by corresponding glycoconjugates with the oligosaccharide chemical structure (Micoli et al, 2019;van der Put et al, 2016;Verez-Bencomo et al, 2004). Beyond vaccine manufacturing, synthetic oligosaccharides have become very advantageous for antigen identification and structure-guided vaccine design (Stefanetti, MacLennan, & Micoli, 2022). Longer polyRha chains were isolated from an E. coli strain genetically modified to express the GAC backbone linked to lipopolysaccharide (LPS) lipid A-core.…”

Exploring the variables influencing the immune response of traditional and innovative glycoconjugate vaccines

“…We have recently reviewed the impact that PS chain length can have on the immune response elicited by glycoconjugate vaccines ( Stefanetti et al, 2022 ). Saccharides can be isolated from bacterial cultures and are often reduced in size through different methodologies in order to simplify manufacture; improve conjugation yields, purification and consistency; and facilitate conjugate characterization.…”

Modeling 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate (CDAP) Chemistry to Design Glycoconjugate Vaccines with Desired Structural and Immunological Characteristics

“…Traditionally, conjugate vaccines are prepared by PS extraction from bacterial fermentation, subsequent purification and chemical binding to the carrier protein [7]. Since very often native PSs have a rather large molecular weight (MW), they are subjected to fragmentation and sizing to obtain shorter saccharides of defined MW range, whose use improves process robustness and simplifies manufacturing and analytical characterization [7,8]. The carbohydrate moiety is chemically linked to the carrier protein, and two main approaches can be used: one based on PS coupling to the protein through activation of the terminal group of the sugar chain and the other based on chemical activation of multiple groups along the PS chain followed by conjugation.…”