Glycoconjugates are a general classification of carbohydrates that are covalently linked to other chemicals such as proteins, peptides, lipids and other compounds. Glycoconjugates are very important molecules in biology and are composed of many different classes, including glycopeptides, peptidoglycans, glycoproteins, glycosides, glycolipids and lipopolysaccharides. They are involved in intercellular interactions, such as intercellular recognition.
As bioinformatics molecules, glycoconjugates can be involved in regulating various life activities in organisms and ensuring their orderly performance. Glycoconjugates served as information carriers have a comprehensive impact on life activities, which are the result of thousands of chemical reactions that cannot be ordered without the guidance of information. Therefore, the study of glycobiology can not only reveal the mechanism of chemical reactions at the molecular level, but also understand the specific roles of different glycoconjugates in living organisms and what important chemical reactions they are involved in.
In addition, the development of glycobiology also has a direct role in the field of health, suggesting that the occurrence and development of diseases are also closely related to glycoconjugates. For example, certain toxin molecules, bacteria and viruses exert their effect through recognition with oligosaccharide chains on host cell, and understanding the details of these oligosaccharide binding sites can contribute to the development of vaccines.
History of glycoconjugate vaccines
Glycoconjugate vaccines are composed of a carbohydrate moiety such as polysaccharide (PS) linked to a protein carrier by covalent coupling, which is one of the safest and most successful vaccines during the last 40 years. Polysaccharides (PS) are T-cell independent antigens able to directly stimulate B cells to produce antibodies, and can be combinated with protein that provide T cell epitopes, which encourage their use as vaccines.
As early as the end of 1970, one PS vaccine was developed and licensed against Neisseria meningitidis, following by other PS vaccines used for different bacterial diseases. However, these vaccines were partially efficacious in adults, but failed to elicit adequate protection in high-risk groups, including infants and children under two years of age. Introduction of the concept of hapten and carrier that were presented in early 20th century, promoting the development of glycoconjugate vaccines. Study reported that saccharides bond to proteins results in enhanced immunogenicity of the saccharide and that saccharide specific antibody concentrations increase after reinjection of the conjugate. Then, the first glycoconjugate vaccine against Haemophilus influenzae type b (Hib) and was licensed in late 1980s. In recent years, various bacterial infections have been addressed by glycoconjugates.
Polysaccharide (PS) are T-cell independent antigens that can directly stimulate B-cell differentiation into plasma cells to produce antibodies through B-cell receptors (BCR). This mechanism is not applicable in infants, where cooperation between B and T cells is necessary for an effective immune response to PS antigens.
In glycoconjugates, the protein carrier provides the T epitopes for T-cell help recruiting, while the B epitopes involved in PS specific B cells are provided by the saccharide moiety. The saccharide binds to BCR, and after internalization, B cells direct the processing of the protein moiety of glycoconjugate in peptides that are presented to carrier specific T cells in association with major histocompatibility complex (MHC) class II molecules. When B cells receive T cell help, they proliferate and differentiate into plasma cells producing antibodies, and into memory B cells, which can rapidly proliferate and differentiate into plasma cells while encounter of specific antigen. An additional mechanism has been shown in studies with GBSIII-protein conjugates. Glycoconjugate is processed into glycan-peptides inside PS specific B cells. The glycan-peptides bind MHC class II through the peptide moiety make the glycan moiety to be exposed and recognized by the T-cell receptor of carbohydrate specific T cell clones which then provide the cognate help to B cells. These mechanisms indicate that glycoconjugate vaccines can induce the T-cell-dependent response and have the potential to be used to elicit immunogenicity in infants.