Peptide Mimics of Bacterial Polysaccarides: Potential for Discriminating Vaccines

Design, synthesis, and immunochemical characterization of a chimeric glycopeptide corresponding to the Shigella flexneri Y O-polysaccharide and its peptide mimic MDWNMHAA

“…[14][15][16][17] In addition to their ability to elicit carbohydrate-binding antibody responses, these peptide mimics should focus the immune responses on particular epitopes since greater discrimination of the peptides for the corresponding antibody-combining sites has been observed, 18 thus minimizing autoimmune reactions with self structures where the original carbohydrate antigens would pose a threat as immunogens. [17][18][19] Shigella flexneri Y is a virulent bacterium that causes bacillary dysentery by invading the colonic mucosa. 20 Screening of a phage-displayed peptide library with an anti-carbohydrate antibody SYA/J6, directed against the O-polysaccharide (Fig.…”

“…21,22 The affinity can be attributed to the considerable unfavorable entropy that arises from a more ordered bound peptide and the immobilization of several water molecules. 17,22 Furthermore, for a peptide to be immunogenic, it might be necessary that a sufficient population of the bound conformation be displayed in the conformational ensemble of the free peptide. 14,15,17 Since the a-helix adopted by NMHAA in the C-terminus of MDWNMHAA is only restricted to the bound conformation and not to that of the free peptide, we hypothesized that MDWNMHAA might not lead directly to a cross-reactive response against the corresponding polysaccharide.…”

“…17,22 Furthermore, for a peptide to be immunogenic, it might be necessary that a sufficient population of the bound conformation be displayed in the conformational ensemble of the free peptide. 14,15,17 Since the a-helix adopted by NMHAA in the C-terminus of MDWNMHAA is only restricted to the bound conformation and not to that of the free peptide, we hypothesized that MDWNMHAA might not lead directly to a cross-reactive response against the corresponding polysaccharide. 14,15,17 Nevertheless, we believed it could still be used in prime-boost strategies to strengthen the immune responses already induced by the polysaccharide epitopes, as shown with a peptide mimic of the capsular polysaccharide of Cryptococcus neoformans.…”

“…14,15,17 Since the a-helix adopted by NMHAA in the C-terminus of MDWNMHAA is only restricted to the bound conformation and not to that of the free peptide, we hypothesized that MDWNMHAA might not lead directly to a cross-reactive response against the corresponding polysaccharide. 14,15,17 Nevertheless, we believed it could still be used in prime-boost strategies to strengthen the immune responses already induced by the polysaccharide epitopes, as shown with a peptide mimic of the capsular polysaccharide of Cryptococcus neoformans. 23 In order to test these hypotheses, we synthesized protein conjugates of the octapeptide 24 and recently evaluated their immunogenicities.…”