Bacterial cell-surface-derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O-acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s). In addition, the ratio of carbohydrate to protein in glycoconjugate vaccines also makes an important contribution in determining the optimum immunological response. This Review article presents the importance of these variables in the development of antibacterial glycoconjugate vaccines and their effects on immune efficacy.
Identifying
the immunogenic moieties and their precise structure
of carbohydrates plays an important role for developing effective
carbohydrate-based subunit vaccines. This study assessed the structure–immunogenicity
relationship of carbohydrate moieties of a single repeating unit of
group A carbohydrate (GAC) present on the cell wall of group A Streptococcus (GAS) using a rationally designed self-adjuvanted
lipid-core peptide, instead of a carrier protein. Immunological evaluation
of fully synthetic glyco-lipopeptides (particle size: 300–500
nm) revealed that construct consisting of higher rhamnose moieties
(trirhamnosyl-lipopeptide) was able to induce enhanced immunogenic
activity in mice, and GlcNAc moiety was not found to be an essential
component of immunogenic GAC mimicked epitope. Trirhamnosyl-lipopeptide
also showed 75–97% opsonic activity against four different
clinical isolates of GAS and was comparable to a subunit peptide vaccine
(J8-lipopeptide) which illustrated 65–96% opsonic activity.
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