Recent mechanistic insights on glycoconjugate vaccines and future perspectives

Vaccination is a key strategy for the control of various infectious diseases. Many pathogens, such as Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), and Neisseria meningitidis produce on their surfaces dense and complex glycan structures, which represent an optimal target for eliciting carbohydrate specific antibodies able to confer protection against those bacteria. Glycoconjugates represent nowadays an important class of efficacious and safe commercial vaccines. It has been known for a long time that covalent linkage of poorly immunogenic carbohydrates to protein is fundamental to provide T cell epitopes for eliciting a memory response of the immune system against the saccharide. However, while the traditional mechanism of action of glycoconjugates has considered peptides generated from the carrier protein to be responsible of T cell help recruitment, only recently evidence of the active involvement of the carbohydrate part in determining the T cell help has been shown. In addition, zwitterionic polysaccharides have been proven to activate the adaptive immune system without further conjugation to protein. Progress in this interface area between chemistry and biology, in combination with novel synthetic and biosynthetic methods for the preparation of glycoconjugates, is opening new perspectives to clarify their mechanism of action and give new insights for the design of improved carbohydrate-based vaccines.