title: The potential of dextran-based glycoconjugates for development of Helicobacter pylori vaccine.
abstract: We have recently demonstrated that synthetic glycoconjugates based on delipidated lipopolysaccharide (LPS) of Helicobacter pylori and containing an α(1-6)-glucan chain induced broadly cross-reactive functional antibodies in immunized animals. To investigate the candidacy of α(1-6)-glucan as an alternative vaccine strategy we prepared glycoconjugates based on dextrans produced by lactic acid bacteria Leuconostoc mesenteroides B512F and consisting of linear α(1-6)-glucan chains with limited branching. Three dextrans with averaged molecular masses of 5,000 Da, 3,500 Da and 1,500 Da, respectively, were modified with a diamino group-containing linker and conjugated to a carrier protein, tetanus toxoid (TT) or diphtheria toxoid (DT), and their immunological properties investigated. The conjugates were immunogenic in both rabbits and mice and induced specific IgG responses against α(1-6)-glucan-expressing H. pylori LPS. Studies performed with post-immune sera of mice and rabbits immunized with dextran-based conjugates demonstrated cross-reactivity with LPS from typeable and non-typeable strains of H. pylori and selected mutants. The post-immune sera from rabbits that received the conjugates exhibited functional activity against α(1-6)-glucan-positive strains of H. pylori. These data provide evidence that dextran-based conjugates may offer a simplified approach to the development of carbohydrate-based vaccines against H. pylori.
authors.affiliation: National Research Council Canada, Ottawa, Ontario, K1A 0R6, Canada, Eleonora.altman@nrc-cnrc.gc.ca.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Altman
authors.forename: Vandana
authors.initials: V
authors.lastname: Chandan
authors.forename: Blair
authors.initials: B
authors.lastname: Harrison
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D003911:Dextrans / Q000737:chemistry / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000737:chemistry; D005936:Glucans / Q000737:chemistry / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007934:Leuconostoc / Q000737:chemistry; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D011817:Rabbits; D013745:Tetanus Toxoid / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D003911:Dextrans; D004168:Diphtheria Toxoid; D005936:Glucans; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate