Team:Slovenia/Conclusions

From 2008.igem.org

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     <li>Antigen-TLR fusions are functional and their localization can be modulated by the selection of transmembrane segment</li>
     <li>Antigen-TLR fusions are functional and their localization can be modulated by the selection of transmembrane segment</li>
<li>Various DNA vaccine constructs have been successfully introduced by electroporation intramuscularly or subcutanelously and expression of the fusion protein in the target tissue <i>in vivo</i> was demonstrated</li>
<li>Various DNA vaccine constructs have been successfully introduced by electroporation intramuscularly or subcutanelously and expression of the fusion protein in the target tissue <i>in vivo</i> was demonstrated</li>
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<li>Two chimeric recombinant protein vaccines showed intense IgG antibody response in mice and immunized sera also reacted with heat-killed <i>H. pylori</i> antigens implying that they recognize epitopes of <i>H. pylori</i>.</li>
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<li>The approach with chimeric flagellins could be used against other flagellated bacteria whose flagellin does not activate innate system (<i>Bartonella, Campylobacter, Borellia</i>...)</li>
<li>The approach with chimeric flagellins could be used against other flagellated bacteria whose flagellin does not activate innate system (<i>Bartonella, Campylobacter, Borellia</i>...)</li>
<li>Could vaccines based on antigen-TLR fusions be used as tumor vaccines as well?</li>
<li>Could vaccines based on antigen-TLR fusions be used as tumor vaccines as well?</li>
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<li>Two chimeric recombinant protein vaccines showed intense IgG antibody response in mice and immunized sera also reacted with heat-killed <i>H. pylori</i> antigens implying that they recognize epitopes of <i>H. pylori</i>.</li>
 
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Revision as of 00:40, 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 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 transactivates 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 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.


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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