Synthesis and immunogenicity of a Helicobacter pylori lipopolysaccharide-based conjugate.

Helicobacter pylori infection in humans is responsible for the onset of severe gastric disorders and a vaccine would be an improvement over current antibiotic-based treatments. Lipopolysaccharide (LPS; O-chain PS→core→lipid A) is a main H. pylori cell wall component, whose O-chain PS exhibits molecular mimicry and therefore any LPS-based vaccine cannot contain O-chain epitopes. Here, the conjugation of de-lipidated H. pylori O:2 LPS to BSA and its immunogenicity in mice is described. IgG antibodies were observed to recognize the LPSs of representative H. pylori serotypes O:1, O:2 and O:5, and more significantly, the core region of H. pylori. This study showed that a monovalent H. pylori LPS conjugate can elicit antibodies that recognize other serotype-specific H. pylori LPSs and specifically the structurally conserved LPS inner-regions.

A novel Helicobacter pylori cell-surface polysaccharide.

Helicobacter pylori bacteria colonize the gastric mucosa of more than half of the world's human population and its infection may instigate a wide spectrum of gastric diseases in the host. At the moment, there is no vaccine against H. pylori, a microorganism recognized as a category 1 human carcinogen, and treatment is limited to antibiotic management. Pioneering antigenic studies carried out by Penner and co-workers, which employed homologous H. pylori antisera specific for cell-surface lipopolysaccharide (LPS), revealed the presence of six distinct H. pylori serotypes (O1 to O6). Subsequent studies have shown that H. pylori serotype O1 expressed LPS with lengthy O-chain polysaccharide (PS) composed of Lewis blood-group structures ('Lewis O-chains'), serotype O3 LPS produced 'Lewis O-chains' attached to a heptoglycan domain, serotype O4 LPS possessed LPS with glucosylated 'Lewis O-chains' and serotype O6 LPS expressed the heptoglycan domain capped by a short 'Lewis O-chain'. These LPSs were terminated at the reducing-end by a core oligosaccharide and lipid A of conserved structures. With the intent of formulating a multivalent H. pylori LPS-based vaccine, we are studying the structural variability of H. pylori cell-surface glycans. Here, we describe the novel LPS structure produced by H. pylori serotype O2 that differed markedly from the typical H. pylori 'Lewis O-chain' structures, in that its main component was an elongated PS composed of alternating 2-, and 3-monosubstituted alpha-D-Glcp residues [-->2)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->]n. These findings revealed the bio-molecular basis for the observed serospecificity of H. pylori serotype O2, and that this unique bacterial PS must be included in the formulation of a multivalent LPS H. pylori vaccine.