<i>H. pylori </i>lipopolysaccharide outer core epitope

摘要

Dextrans produced by lactic acid bacteria Leuconostoc mesenteroides and consisting of linear α1,6-glucan chains modified with short side-chains composed of consecutive α1,6-linked glucose residues were linked to a carrier protein. Three dextrans, namely Dextran-5K, Dextran-3.5K and Dextran-1.5K, with molecular masses of 5,000 Da, 3,500 Da and 1,500 Da, respectively, were modified with a diamino group-containing linker, followed by the introduction of maleimido functionality and conjugation to thiolated tetanus toxoid (TT), yielding Dextran-5K-TT, Dextran-3.5K-TT and Dextran-1.5K-TT conjugates. Studies performed with post-immune sera of mice and rabbits immunized with dextran-based glycococonjugates demonstrated cross-reactivity with LPS from typeable and non-typeable H. pylori strains and selected mutants. The post-immune sera from rabbits that received the conjugates exhibited functional activity against α1,6-glucan-positive strains of H. pylori, 26695 HP0826::Kan mutant lacking the O-chain component and corresponding wild-type strain 26695. This study provides the proof that α1,6-glucan-based conjugates provide an alternative vaccine strategy for protection against H. pylori infections.

主权项

1. An immunogenic conjugate comprising an isolated dextran conjugated to a linker molecule, an isolated protein carrier, or a combination thereof, wherein the isolated dextran comprises a substantially linear alpha 1,6-glucan chain of 6 to 14 consecutive glucose residues and has an average molecular weight between 1.5 kDa and 6.5 kDa and wherein the conjugate, upon administration to a mammal, elicits alpha 1,6-1inked glucan-specific antibodies that are cross-reactive with the lipopolysaccharide (LPS) of Heliobacter pylori (H. pylori) and that are bactericidal against H. pylori.