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

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Allergic diseases bite the dust

Scientists have moved one step further in the treatment of allergic diseases using plasmid constructs to deliver allergen encoding vaccines.

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Genetic or DNA vaccines have gained acceptance as a potent means of providing protective immunity against infective agents in all species - from fish to primates. In response to the escalation of allergic diseases, research on plasmid DNA encoding proteins from allergens promises relief to the sufferers of allergic diseases such as asthma. Scientists working with the European project ALLDNAVAC focused their research on how the allergen encoding vaccines modulated immunological mechanisms. Probably the two most common causes of allergy were targeted, the house dust mite and the pollen of Parietaria, a widely distributed flowering plant. Human allergic disorders are characterised by the proliferation of T helper Type 2 (Th2) cells and B cells, both of which are important in immune reactions. However, these cells can form an important part of the allergic inflammatory response. Project partners worked on the design and evaluation of novel DNA vaccines in terms of their ability to inhibit allergic Th2-mediated responses. At Novartis Vaccines & Diagnostics S.r.l. in Italy, the team worked specifically on a plasmid DNA construct developed within the company. The pCMV plasmid, so-called because of the cytomegalovirus (CMV) component was used as the vector. The resulting construct was pCMVDerp1 cyt which contains the house dust mite gene Derp1. The researchers found that the Derp1 gene was encoded within in vitro transiently transfected cells. One practical modification was that the Derp1 gene was cloned directly downstream from the CMV promoter. This prevented secretion of the Derp1 protein and kept it within the cytoplasm of the cell. Further research on this plasmid construct will enable a thorough study of the plasmid's ability to invoke an immune response and DNA vaccines.

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