Novel strategies for development of next-generation glycoconjugate vaccines

Most bacterial pathogens are decorated with surface glycans called capsular polysaccharides (CPSs). Each CPS has a unique structure that is distinctively recognized by our immune cells. These polysaccharides are important vaccine candidates given that they are located on the surface of pathogens, are easily accessible by the immune system, and often result in formation of protective antibodies. To induce CPS specific adaptive immune response (i.e., T cell-mediated B cell response), CPSs are conjugated with carrier proteins, and the conjugation products are called glycoconjugate vaccines. Immunization with glycoconjugate vaccines has had significant health benefits in controlling infections caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. However, owing to insufficient understanding of their immune activation mechanisms, glycoconjugate vaccines have been designed and synthesized empirically. In recent years, we have witnessed important advancements in the glycoconjugate vaccine field: the discovery of the mechanism of action for glycoconjugate vaccines, a novel in vivo conjugation strategy, and progress in the use of novel carriers. These studies will be reviewed in detail herein.