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      Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

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          Abstract

          Advantages of DNA vaccination against infectious diseases over more classical immunization methods include the possibilities for rapid manufacture, fast adaptation to newly emerging pathogens and high stability at ambient temperatures. In addition, upon DNA immunization the antigen is produced by the cells of the vaccinated individual, which leads to activation of both cellular and humoral immune responses due to antigen presentation via MHC I and MHC II molecules. However, so far DNA vaccines have shown most efficient immunogenicity mainly in small rodent models, whereas in larger animals including humans there is still the need to improve effectiveness. This is mostly due to inefficient delivery of the DNA plasmid into cells and nuclei. Here, we discuss technologies used to overcome this problem, including physical means such as in vivo electroporation and co-administration of adjuvants. Several of these methods have already entered clinical testing in humans.

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          Most cited references85

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          An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.

          Cytoplasmic DNA triggers activation of the innate immune system. Although 'downstream' signaling components have been characterized, the DNA-sensing components remain elusive. Here we present a systematic proteomics screen for proteins that associate with DNA, 'crossed' to a screen for transcripts induced by interferon-beta, which identified AIM2 as a candidate cytoplasmic DNA sensor. AIM2 showed specificity for double-stranded DNA. It also recruited the inflammasome adaptor ASC and localized to ASC 'speckles'. A decrease in AIM2 expression produced by RNA-mediated interference impaired DNA-induced maturation of interleukin 1beta in THP-1 human monocytic cells, which indicated that endogenous AIM2 is required for DNA recognition. Reconstitution of unresponsive HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1beta showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.
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            DNA vaccines: ready for prime time?

            Since the discovery, over a decade and a half ago, that genetically engineered DNA can be delivered in vaccine form and elicit an immune response, there has been much progress in understanding the basic biology of this platform. A large amount of data has been generated in preclinical model systems, and more sustained cellular responses and more consistent antibody responses are being observed in the clinic. Four DNA vaccine products have recently been approved, all in the area of veterinary medicine. These results suggest a productive future for this technology as more optimized constructs, better trial designs and improved platforms are being brought into the clinic.
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              Recognition of cytosolic DNA activates an IRF3-dependent innate immune response.

              Nucleic acid recognition upon viral infection triggers type I interferon production. Viral RNA is detected by both endosomal, TLR-dependent and cytosolic, RIG-I/MDA5-dependent pathways. TLR9 is the only known sensor of foreign DNA; it is unknown whether innate immune recognition of DNA exists in the cytosol. Here we present evidence that cytosolic DNA activates a potent type I interferon response to the invasive bacterium Listeria monocytogenes. The noninvasive Legionella pneumophila triggers an identical response through its type IV secretion system. Activation of type I interferons by cytosolic DNA is TLR independent and requires IRF3 but occurs without detectable activation of NF-kappaB and MAP kinases. Microarray analyses reveal a unique but overlapping gene-expression program activated by cytosolic DNA compared to TLR9- and RIG-I/MDA5-dependent responses. These findings define an innate immune response to DNA linked to type I interferon production.
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                Author and article information

                Journal
                Clin Exp Vaccine Res
                Clin Exp Vaccine Res
                CEVR
                Clinical and Experimental Vaccine Research
                The Korean Vaccine Society
                2287-3651
                2287-366X
                January 2015
                30 January 2015
                : 4
                : 1
                : 1-10
                Affiliations
                Department of Immunology, Fraunhofer-Institute for Cell Therapy and Immunology, Leipzig, Germany.
                Author notes
                Corresponding author: Sebastian Ulbert, PhD. Department of Immunology, Fraunhofer-Institute for Cell Therapy and Immunology, Perlickstraβe 1, 04103 Leipzig, Germany. Tel: +49-341-35536-2106, Fax: +49-341-35536-82106, sebastian.ulbert@ 123456izi.fraunhofer.de

                *These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7593-4914
                http://orcid.org/0000-0001-5910-3643
                Article
                10.7774/cevr.2015.4.1.1
                4313101
                25648133
                20cb96e0-f3d8-41c4-8b9a-69282786d800
                © Korean Vaccine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 November 2014
                : 30 November 2014
                : 31 December 2014
                Categories
                Special Article

                dna vaccines,gene transfer techniques,immunologic adjuvants,infection

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