Team:Slovenia/Conclusions

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       <ul>
       <ul>
         <li>Chimeric flagellins were produced in bacteria, purified and characterized</li>
         <li>Chimeric flagellins were produced in bacteria, purified and characterized</li>
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         <li>Engineered flagellins activate TLR5 as opposed to the native <i>H. pylori</i> flagellin</li>
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         <li>Engineered <i>H. pylori</i> flagellins activate TLR5 as opposed to the native <i>H. pylori</i> flagellin</li>
         <li>Three different implementations of chimeric flagellin vaccines were prepared</li>
         <li>Three different implementations of chimeric flagellin vaccines were prepared</li>
         <li>Chimeric flagellin is localized at the bacterial surface</li>
         <li>Chimeric flagellin is localized at the bacterial surface</li>
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         <li>DNA construct based on chimeric flagellin transactivates TLR5 on neighboring cells (demonstration of the feasibility of introduction of DNA into the epithelial cells to activate the underlying dendritic cells)</li>
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         <li>DNA construct based on chimeric flagellin causes transactivation of TLR5 on neighboring cells (demonstration of the <b>feasibility of introduction of DNA into the epithelial cells to activate the underlying dendritic cells)</b></li>
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       </ul>
     </li>
     </li>

Revision as of 00:57, 30 October 2008

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Conclusions


Achievements

  • We have demonstrated the power of modular building blocks approach of synthetic biology (IMMUNOBRICKS) for the rational design of vaccines
  • We have designed a new type of vaccine against H. pylori based on the chimeric flagellin that combines activation of innate and adaptive immunity within the same molecule
    • Chimeric flagellins were produced in bacteria, purified and characterized
    • Engineered H. pylori flagellins activate TLR5 as opposed to the native H. pylori flagellin
    • Three different implementations of chimeric flagellin vaccines were prepared
    • Chimeric flagellin is localized at the bacterial surface
    • DNA construct based on chimeric flagellin causes transactivation of TLR5 on neighboring cells (demonstration of the feasibility of introduction of DNA into the epithelial cells to activate the underlying dendritic cells)
  • Antigen-TLR fusions are functional and their localization can be modulated by the selection of transmembrane segment
  • 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
  • Two chimeric recombinant protein vaccines showed an intense IgG antibody response in mice and immunized sera also reacted with live and heat-killed H. pylori implying that they recognize epitopes of H. pylori.


What remains to be done ?
  • Complete the animal studies: demonstrate the prophilactic 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……
  • 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
  • Analyze different combinations of antigen-TLRs to obtain optimal immune stimulation (TLR synergy)
  • Repeat all experiments with many controls, in comparison to currently used adjuvants etc
  • ... ... ars longa, vita brevis


Prospects
  • Functional vaccine against H. pylori would be definitely welcome
  • The approach with chimeric flagellins could be used against other flagellated bacteria whose flagellin does not activate innate system (Bartonella, Campylobacter, Borellia...)
  • Could vaccines based on antigen-TLR fusions be used as tumor vaccines as well?




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