Taken together, a wealth of published pre-clinical studies in small and large animal models appears to suggest that muscle is a practical, effective, and safe target for genetic vaccines based on different vector platforms. However, complexity of vaccine immunology, interactions between host protective immunity and viral immunopa-thology as well as the lack of full correlations between vaccine efficacy and safety data generated from currently available animal models and human trials strongly argue for the necessity to go back to the drawing board and basic research to further delineate all of those aspects for genetic vaccines before rushing into human trials. Depending on the pathogenesis of microbial infections and route of infectious disease transmission, some alternative routes of vaccination such as mucosal directed genetic vaccines should also be further explored for which AAV based vaccine may be advantageous because of its relative hardness and resistance to temperature, pH extremes, and solvents (Berns and Hauswirth 1979; During et al. 2000).

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