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DNA vaccines have shown promise in small animal models, and are effective at generating anti\u2010viral T cell\u2010mediated immune responses; however, they have proved to be poorly immunogenic in clinical trials. We propose that the induction of necrosis will enhance the immune response to vaccine antigens encoded by DNA vaccines, as necrotic cells are known to release a range of intracellular factors that lead to dendritic cell (DC) activation and enhanced cross\u2010presentation of antigen. Here we provide evidence that induction of cell death in DNA vaccine\u2010targeted cells provides an adjuvant effect following intradermal vaccination of mice; however, this enhancement of the immune response is dependent on both the mechanism and timing of cell death after antigen expression. We report that a DNA vaccine encoding the cytolytic protein, perforin, resulted in DC activation, enhanced broad and multifunctional CD8 T\u2010cell responses to the HIV\u20101 antigen GAG and reduced viral load following challenge with a chimeric virus, EcoHIV, compared with the canonical GAG DNA vaccine. This effect was not observed for a DNA vaccine encoding an apoptosis\u2010inducing toxin, DTa, or when the level of perforin expression was increased to induce cell death sooner after vaccination. Thus, inducing lytic cell death following a threshold level of expression of a viral antigen can improve the immunogenicity of DNA vaccines, whereas apoptotic cell death has an inhibitory effect on the immune response.<\/jats:p>","DOI":"10.1038\/icb.2013.93","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T10:33:32Z","timestamp":1386671612000},"page":"359-367","source":"Crossref","is-referenced-by-count":25,"title":["Induction of antigen\u2010positive cell death by the expression of Perforin, but not DTa, from a DNA vaccine enhances the immune response"],"prefix":"10.1111","volume":"92","author":[{"given":"Tessa","family":"Gargett","sequence":"first","affiliation":[{"name":"Virology Laboratory, Discipline of Surgery, University of Adelaide, Basil Hetzel Institute for Translational Medicine Adelaide South Australia 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