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In an effort to enhance the potency of DNA vaccines, we have developed a new strategy to increase antigen presentation by dendritic cells, one that results in markedly improved cytotoxic T-lymphocyte responses, antibody production, and antitumor effects in vivo. Here, we present the rationale and design of a vaccine encoding a secreted antigen-heat shock protein 70 fusion molecule, targeted to the...
Genetic immunization strategies have largely focused on the use of ''naked'' plasmid DNA or the gene gun. However, there remains a clear need to further improve the efficiency and/or cost of potential DNA vaccines. The theoretical basis of our research is to rationally design genetic immunization methodologies for nanoparticle-based delivery systems of plasmid DNA, perhaps in combination with already...
The skin has evolved as a barrier to prevent external agents, including pathogens, from entering the body. It has a complex and efficient immune surveillance system, which includes Langerhans cells and dendritic cells. By targeting the body's natural defense system, skin-DNA immunization attempts to produce an efficient immune response. Nucleic acid vaccines provide DNA for protein expression in a...
DNA vaccines have become a reliable and major means to elicit immune responses in the past decade. We and others have attempted to obtain stronger, more long lasting, and optimized immune responses, subsequent to the pioneering works demonstrating the ability of plasmid DNA to raise specific immune responses. Advances in molecular biology and biotechnology allow the application of various adjuvants,...
Delivery of antigen-encoding genes by nucleic acid vaccine vectors offers tremendous advantages in power and flexibility over conventional antigen delivery systems. Of the many forms of nucleic acid vaccine that can be constructed, circular DNA plasmids are the simplest. In this article, we consider the components that make up a generic DNA plasmid vaccine. We discuss some of the issues encountered...
DNA vaccine strategies can differ greatly, with significant effects on the outcome of immunization. In this article, we discuss plasmid design strategies and vaccine regimens. Effectiveness against a pathogen can be affected by the choice of antigen and inclusion of multiple antigens. Gene expression and the resulting immune response can be improved by gene modification and choice of promoters. In...
DNA vaccines represent a new approach to the control of infectious disease. Both cellular and humoral immune responses are induced without the attendant concerns associated with live, attenuated vaccines. The vast majority of DNA vaccines are delivered by parental routes, which rarely elicit immune responses at the mucosal epithelia, the primary sites of pathogen transmission. In view of the importance...
Pathogenic bacteria still represent a major threat to human health worldwide and the need for new vaccines is great. Virulence factors, particularly surface-located molecules, often make good vaccine targets because they are essential for access to their niche within the host. The advent of whole-genome sequencing of bacterial pathogens has revolutionized the methods by which these organisms are studied...
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