Immunogenicity Assessment of Cell Wall Carbohydrates of Group A <i>Streptococcus</i> via Self-Adjuvanted Glyco-lipopeptides
Farjana Khatun, Charles C. Dai, Tania Rivera-Hernández, Waleed M. Hussein, Zeinab G. Khalil, Robert J. Capon, István Tóth, Rachel J. Stephenson
Abstract
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.