Patch Immunization: Transcutaneous Vaccination for the Cholera Toxin and Optimization of Immunization Cycles

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The main point of this analysis was to investigate the diffusion of the cholera vaccination through specific layers of the skin. The antigen was initially modeled through the skin directly to the blood stream. The antigen was also modeled with the presence of a network of Langerhans cells. There was a smooth concentration profile in the skin after one week of patch exposure in the absence of the LC network. However, there was discontinuity in the concentration profile when the LC network was present. The LC network functioned as a large enough sink term that the flux into the bloodstream was virtually zero. Therefore, we concluded that the LC network alone can create a cutaneous immune response. The LC network was enhanced with the presence of Imiquimod, a typical immune response modifier. The modifier increased the activity of the LC network, thus increasing the reaction rate of the LC cells. With Imiquimod there was a sharper discontinuity in the concentration profile at the LC network and the antigen flux into the blood stream is zero.
The most effective enhancer tested was the MEMs microneedles, which increased the porosity of the skin and thus the diffusivity of the antigen through the skin. Contour plots of the skin showed absolute diffusion and consumption of the antigen into the LC network, while only partial consumption with the other enhancers tested. Concentration gradients were present in the ultrasonically and photo mechanically enhanced skin because they had weaker enhancing capabilities compared to the MEMs needles. The MEMs needles are the most effective in mass transfer, but are also the most evasive. Vaccines are usually given in cycles to increase the concentration of the antigen in the skin and bloodstream. When the patch was applied to the skin with no enhancer, the maximum concentration was achieved after 2.3 days. However, the maximum concentration in the skin is achieved sooner with the various adjuvants. For example, when the patch is applied with MEMs needles, the maximal concentration is achieved in the skin only after 1.2 hours of exposure. Immunization cycles presented in Glenn et al were simulated to determine the approximate concentration of the antigen at the center of the skin needed for an immune response. This concentration is 0.0038 mol/m^3. Therefore, it was assumed that if the concentration in the skin is close to this value, then an immune response will be initiated. The immunization cycles for each adjuvant used were then optimized.

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