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| - | Achievements
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| - | · We have demonstrated the power of modular building blocks approach of synthetic biology (IMMUNOBRICKS) for the rational design of vaccines
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| - | · We have designed a new type of vaccine against H. pylori based on chimeric flagellin that combines activation of innate and adaptive immunity in the same molecule
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| - | · Chimeric flagellins were produced in bacteria, purified and characterized
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| - | · Engineered flagellins activate TLR5 as opposed to the native H. pylori flagellin
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| - | · three different implementations of chimeric flagellin vaccines were prepared
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| - | · chimeric flagellin is localized at the bacterial surface
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| - | · DNA construct based on chimeric flagellin activates TLR5 on neighboring cells (demonstration of the feasibility of introduction of DNA into epithelial cells to activate underlying dendritic cells)
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| - | · Antigen-TLR fusions are functional and their localization can be modulated by the selection of transmembrane segment
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| - | · Various DNA vaccine constructs have been successfully introduced by electroporation intramuscularly or subcutanelously and expression of the fusion protein in the target tissue in vivo was demonstrated
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| - | What remains to be done ?
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| - | · Complete animal studies: demonstrate the profilactic efficiency of our vaccines to prevent colonization, and therapeutic value to eradicate existing infection as well as evaluate effects of vaccinations on histology of gastric mucosa……
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| - | · Demonstrate the efficiency of bacterial implementation of flagellin-like vaccine on lyophilized bacterial ghosts (more safe and stable vaccine), particularly for oral and mucosal vaccination – prospects for application in third world countries
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| - | · Analyze different combinations of antigen-TLRs to obtain optimal immune stimulation (TLR synergy)
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| - | · Repeat all experiments with many controls, in comparison to currently used adjuvants etc
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| - | Prospects
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| - | · Functional vaccine against H. pylori would be definitely welcome
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| - | · The approach with chimeric flagellins could be used against other flagellated bacteria whose flagellin does not activate innate system (Bartonella, Campylobacter, Borellia...)
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| - | · Could vaccines based on antigen-TLR fusions be used as tumor vaccines as well?
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| - | · ... ... (ars longa, vita brevis)
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| - | · Two chimeric recombinant protein vaccines showed intense IgG antibody response in mice and immunized sera also reacted with heat-killed H. pylori antigens implying that they recognize epitopes of H. pylori.
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