Bacterial infections are a serious health concern and are responsible for millions of illnesses and deaths each year in communities around the world. Vaccination is an important public health measure for reducing and eliminating this burden, and regions with comprehensive vaccination programs have achieved significant reductions in infection and mortality. This is often accomplished by immunization with bacteria-derived carbohydrates, typically in conjunction with other biomolecules, which induce immunological memory and durable protection against bacterial human pathogens. For many species, however, vaccines are currently unavailable or have suboptimal efficacy characterized by short-lived memory and incomplete protection, especially among at-risk populations. To address this challenge, new tools and techniques have emerged for engineering carbohydrates and conjugating them to carrier molecules in a tractable and scalable manner. Collectively, these approaches are yielding carbohydrate-based vaccine designs with increased immunogenicity and protective efficacy, thereby opening up new opportunities for this important class of antigens. In this chapter we detail the current understanding of how carbohydrates interact with the immune system to provide immunity; how glycoengineering, especially in the context of glycoconjugate vaccines, can be used to modify and enhance immune responses; and current trends and strategies being pursued for the rational design of next-generation glycosylated antibacterial vaccines. Graphical Abstract.
Keywords: Adaptive immune response; Bacterial vaccines; Carbohydrate antigens; Glycoconjugate vaccines; Glycoimmunology; Immunity; Oligosaccharides; Polysaccharides.