Team:Slovenia/Conclusions

From 2008.igem.org

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<strong>Achievements <br /><br /></strong>
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<strong><font size="4">Achievements <font size="2"><br /><br /></strong>
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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 <b>an intense IgG antibody response in mice</b> and <b>immunized sera also reacted with live and heat-killed <i>H. pylori</i><b> implying that they recognize epitopes of <i>H. pylori</i>.</li>
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<li>Two chimeric recombinant protein vaccines showed <b>an intense IgG antibody response in mice</b> and <b>immunized sera also reacted with live and heat-killed <i>H. pylori</i></b> implying that they recognize epitopes of <i>H. pylori</i>.</li>
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<strong>What remains to be done ?<br /><br /></strong>
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<strong><font size="4">What remains to be done ?<font size="2"><br /><br /></strong>
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   <li>Analyze different combinations of antigen-TLRs to obtain optimal immune stimulation (TLR synergy)</li>
   <li>Analyze different combinations of antigen-TLRs to obtain optimal immune stimulation (TLR synergy)</li>
<li>Repeat all experiments with many controls, in comparison to currently used adjuvants etc</li>
<li>Repeat all experiments with many controls, in comparison to currently used adjuvants etc</li>
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<li>... ... (ars longa, vita brevis)</li>
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<li>... ... ars longa, vita brevis</li>
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<strong>Prospects<br /><br /></strong>
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<strong><font size="4">Prospects<font size="2"><br /><br /></strong>
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<li>Functional vaccine against <i>H. pylori</i> would be definitely welcome</li>
<li>Functional vaccine against <i>H. pylori</i> would be definitely welcome</li>

Revision as of 00:54, 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 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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