Glycovaccinology : The design and Engineering of Carbohydrate-Based Vaccine Components

Vaccines remain one of the cornerstones of preventive medicine, providing against a wide range of diseases by inducing humoral and/or cellular immunity. Among the many possible antigen candidates for subunit vaccine development, carbohydrates are desirable due to their ubiquitous presence on the surface of all living cells, viruses and parasites, and their known interactions with innate and adaptive immune cells. Several licensed vaccines use bacterial cell surface carbohydrates as antigens to induce antigen-specific plasma cells that secrete protective antibodies and the development of memory T and B cells.

Bacterial cell surface polysaccharides. Carbohydrate motifs on the surface of bacteria accessible to cells of the immune system are useful targets for raising a protective immune response. Some, including CPS and glycoproteins, are ubiquitous and present on many bacterial species. Other glycan structures are found primarily in Gram-negative bacteria, such as LOS and LPS, or Gram-positive bacteria, such as wall teichoic acid (WTA) and lipoteichoic acid (LTA). Some glycans, including lipoarabinomannan and arabinogalactan, are unique to mycobacteria, a subclass of Gram-positive bacteria. Peptidoglycan (PG) is present on the surface of Gram-positive but not Gram-negative bacteria, where it is instead found in the periplasmic space (Per) between the inner membrane (IM) and outer membrane (OM).

Carbohydrates have also attracted attention in other aspects of vaccine development, such as adjuvants that activate innate immune responses or target specific immune cells. In addition, carbohydrates can act as immunomodulators, dampening unwanted humoral immune responses against whole protein antigens or specific conserved regions on antigenic proteins. In this review, the authors highlight how the interplay between carbohydrates and the adaptive and innate arms of the immune response is guiding the development of glycans as vaccine components that act as antigens, adjuvants, and immunomodulators. They also discuss how advances in synthetic glycobiology are enabling the design, engineering, and production of this new generation of carbohydrate-containing vaccines.