Chemoenzymatic synthesis of an alpha-1,6-glucan-based conjugate vaccine against Helicobacter pylori

In this study, we investigated the utility of glycoconjugates based on a linear alpha-1,6-glucan chain synthesized using a recombinant alpha-1,6-glucosyltransferase from the 26695 strain of Helicobacter pylori. Capillary electrophoresis-mass spectrometry analysis confirmed the main product to contain 9-10 sequentially added alpha-1,6-linked glucose residues. This was consistent with a length of alpha-1,6-glucan structure present in the outer core region of H. pylori lipopolysaccharide (LPS) from strains 26695 and 26695 HP0826::Kan. The synthetic alpha-1,6-glucan was conjugated to either bovine serum albumin or tetanus toxoid and immunological properties of resultant glycoconjugates investigated. The conjugates were immunogenic in rabbits and mice and induced strong and specific IgG responses against purified LPS from typeable and nontypeable alpha-1,6-glucan-positive H. pylori strains. Furthermore, the post-immune sera from rabbits that received the conjugates were bactericidal and cross-reacted with selected clarithromycin-resistant and clarithromycinsusceptible clinical isolates of H. pylori. This technology offers a novel approach to the design of a synthetic carbohydrate-based vaccine against H. pylori.

Automated summary

This study investigated the use of glycoconjugates based on a recombinant alpha-1,6-glucosyltransferase from Helicobacter pylori to synthesize a linear alpha-1,6-glucan chain. The conjugates showed immunogenicity in rabbits and mice, inducing strong IgG responses against purified LPS from H. pylori strains. The post-immune sera from rabbits also exhibited bactericidal activity against selected clinical isolates of H. pylori.