Immunogenicity evaluation of semisynthetic α-(1 → 3)-D,D-heptoglycan conjugates for Helicobacter pylori vaccine development.

Helicobacter pylori is a Gram-negative bacterium that infects nearly half the global population and is associated with a range of gastric diseases, including gastric cancer. The lipopolysaccharides on the surface of H. pylori are immunogenic and have been regarded as attractive targets for carbohydrate-based vaccines. In this study, two semisynthetic glycoconjugates, CRM197-1 and CRM197-4, were prepared by conjugating a α-(1  →  3)-D,D-hepto-disaccharide and a α-(1  →  3)-D,D-hepto-pentasaccharide, respectively, with carrier protein CRM197. Compared with CRM197-1, CRM197-4 elicited a more robust antigen-specific IgG response in rabbits and exhibited stronger binding affinities to synthetic heptoglycans. Moreover, sera from rabbits immunized with CRM197-4 showed pronounced recognition of native O6 H. pylori LPS in microarray analysis. These findings identify CRM197-4, featuring a longer heptoglycan chain, as a promising candidate for further development of heptoglycan-conjugate vaccines against H. pylori infection.