Together with hygiene, vaccines have made possible a great revolution in the 20th century, saving millions of lives. Due to the increase of antibiotic resistance, we can expect that in the next years vaccination will be applied to tackle unmet medical needs, and for prevention of microbial infections caused by antibiotic resistant microorganisms, pandemic infections, and diseases for travelers to areas afflicted by diseases no longer present in the country of origin. Glycoconjugate vaccines represent one of the keys for success of vaccination in children. Dramatic reduction of the effect of infections from Streptococcus pneumoniae following the introduction of the anti-pneumococcal represents one of the most important results obtained in the context of glycovaccine field.
Bacterial polysaccharides, if administered unconjugated, are T-cell-independent antigens and cannot be processed by antigen-presenting cells (APCs). They can induce B-cells to differentiate into plasma cells, leading to secretion of low affinity antibodies, predominantly IgM with some subsequent isotype switch to IgG, but without the formation of a persistent memory B-cell pool. When polysaccharides are covalently linked to proteins, the resulting conjugates bind to polysaccharide-specific receptors on the surface of APCs. Following uptake and protein digestion, the released peptide epitopes are exposed onto the surface in association with MHCII and presented to CD4+ T cells. Peptide/MHCII-activated T cells produce cytokines to stimulate B cell maturation to memory cells and induce immunoglobulin class switching from IgM to polysaccharide-specific IgG, so that upon exposure to the same carbohydrate, be it an invading microorganism or as a vaccine boost, specific B-cells can proliferate. Definitely the covalent linkage to proteins render the carbohydrates able to evoke a T cell memory response, resulting in an effective immune response.
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