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Comprehensive Summary: Helicobacter pylori (H. pylori) infection is a threat to human health. The lipopolysaccharide (LPS) O‐antigen holds promise for developing vaccines. It is meaningful to explore the immunological activity of oligosaccharides with different lengths and frameshifts for antigen development. Herein, a glycan library of H. pylori O2 O‐antigen containing eight fragments is constructed. After screening with anti‐H. pylori O2 LPS sera and patients' sera by glycan microarray, the disaccharide HPO2G‐2b and trisaccharide HPO2G‐3a show strong antigenicity and then are separately conjugated with carrier protein CRM197. Both glycoconjugates elicit a robust immunoglobulin G (IgG) immune response in rabbits. The anti‐HPO2G‐3a IgG antibodies possess a much stronger binding affinity with the LPS and bacteria of H. pylori O2 than the anti‐HPO2G‐2b IgG antibodies. There is no cross‐reaction between both sera IgG antibodies with LPS and bacteria of H. pylori O1, O6, and E. coli. The results demonstrate the trisaccharide HPO2G‐3a is a promising candidate for H. pylori vaccine development. [ABSTRACT FROM AUTHOR]

The gut pathogen Clostridium bolteae has been associated with the onset of autism spectrum disorder (ASD). To create vaccines against C. bolteae, it is important to identify exact protective epitopes of the immunologically active capsular polysaccharide (CPS). Here, a series of C. bolteae CPS glycans, up to an octadecasaccharide, was prepared. Key to achieving the total syntheses is a [2+2] coupling strategy based on a β‐d‐Rhap‐(1→3)‐α‐d‐Manp repeating unit that in turn was accessed by a stereoselective β‐d‐rhamnosylation. The 4,6‐O‐benzylidene‐induced conformational locking is a powerful strategy for forming a β‐d‐mannose‐type glycoside. An indirect strategy based on C2 epimerization of β‐d‐quinovoside was efficiently achieved by Swern oxidation and borohydride reduction. Sequential glycosylation, and regioselective and global deprotection produced the disaccharide and tetrasaccharide, up to the octadecasaccharide. Glycan microarray analysis of sera from rabbits immunized with inactivated C. bolteae bacteria revealed a humoral immune response to the di‐ and tetrasaccharide, but none of the longer sequences. The tetrasaccharide may be a key motif for designing glycoconjugate vaccines against C. bolteae. [ABSTRACT FROM AUTHOR]

The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo‐polysaccharide (LPS) O‐antigens that contain Lewis determinant oligosaccharides and unique dd‐heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O‐antigen containing a terminal Ley tetrasaccharide, a unique α‐(1→3)‐, α‐(1→6)‐, and α‐(1→2)‐linked heptoglycan, and a β‐d‐galactose connector, by an [(2×1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O‐antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of the dd‐heptoglycan and Ley tetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α‐(1→3)‐linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6. [ABSTRACT FROM AUTHOR]