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Immunisation against H. pylori is an attractive option for antibiotic resistance and reinfection situations. Strain genetic heterogeneity, and low immunogenicity of protein antigens and DNA alone are nonetheless obstacles to this approach. We developed multigenic H. pylori DNA-nanoparticle and protein-nanoparticle vaccines based on pathogenic relevance. Six antigens were chosen for the vaccine construction: CagA, VacA, HpaA, UreB, HomB and GroEL. Different combinations of CS/DS and CS/Alg /TPP nanoparticles with DNA and chimeric proteins were produced as vaccine systems. Immune responses were evaluated after i.m. and oral immunisation of BALB/c mice. Oral vaccination successfully stimulated mucosal immunity while i.m. immunisation efficiently elicited a more equilibrated cellular/humoral immune response.