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Our Funds at Work
Jan Peter Dutz, MD, University of British Columbia, Vancouver, BC.
The skin is the first boundary between pathogens and the body. Dendritic cells (DC) are specialized cells that activate the immune system and are found in the skin. These cells ingest microbes and are unique in activating killer T cells that kill microbes. In previous work we have shown that a topical cream composed of short specific DNA sequences (CpG repeats) can enhance the generation of killer T cells in response to injected vaccines. Currently, the mechanisms of how such a cream activates the immune system to induce killer T cells and how the DC interactions enhance the immune responses to vaccines are unclear. The overall purpose of this project is to determine these mechanisms in order to improve the effectiveness of standard vaccines. We propose that the topical cream activates skin DCs indirectly by causing local inflammation. We propose that the inflammation results in activated DC in the local lymph nodes thus increasing vaccine efficacy. To confirm this, we will use mice as an animal model and a protein called ovabumin as the vaccine component. Immune responses in mice that are genetically altered in their ability to respond to the active cream components will be used to pinpoint the locus of action of the cream. This work will provide insights into new methods to optimize current vaccine strategies. This is of benefit in the fight against both infection and cancer.
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