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Allergen-derived DNA vaccines: mechanisms involved in mouse and human models

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Alternative pathways lead to allergic response assay

Toll-like receptors (TLRs) have the potential to change the nature of an immune response in vitro. A European project has researched into using TLRs as the basis of a simple assay for testing the extent of an immune reaction.

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Many disorders are thought to be linked to allergic responses. Finding potential therapies is highly alluring, both in terms of relief for the millions of sufferers and progress in the biopharmaceutical arena. The European project ALLDNAVAC ploughed its resources into research on developing novel DNA vaccines, one possible treatment for allergies. Overall, the objective of the project consortium was to investigate the efficiency and side-effects of new plasmid DNA vaccines against human allergic diseases. The project team at the University of Firenze, Italy developed a simple, effective assay to measure the extent of the immune response to a given vaccine. The immune response is a cascade of events that can be manipulated biochemically at various key stages. When an allergic reaction takes place, an allergen presenting cell (APC) displays the allergen to a T cell which can then mature to form a T helper (Th) cell. Harnessing this pathway, the scientists applied toll-like receptors (TLRs) agonists, including Resiquimod and Imiquimod in vitro to activate APCs. The presenting cells then induced the overproduction of pro-inflammatory cytokines. Together with the allergen, these factors switched the production of Th2 cells from allergic patients to T cells that produced interferon-gamma (IFN-gamma). The presence of IFN-gamma constitutes a simple assay which can therefore be used to gauge the extent of a Th2 immune response in a patient. An extension of this research could be in the development of therapies for diseases involving Th2 lymphocytes and may well form the basis for other novel vaccines.

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