DNA Vaccines

McDonnell, W. Michael; Askari, Frederick K.

doi:10.1056/nejm199601043340110

Cited by 155 publications

(58 citation statements)

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“…CpG DNA conjugate vaccines have been shown to induce strong innate immune responses and clinical trials of vaccines that include CpG DNA are in progress (48). In addition, HIV gp120: CpG DNA conjugate vaccines have been developed and tried in animal models and were shown to induce strong gp120-specific immune responses (49).…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal RepeatTrans-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Equils

Schito

Karahashi

et al. 2003

The Journal of Immunology

100

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Opportunistic infections are common in HIV-infected patients; they activate HIV replication and contribute to disease progression. In the present study we examined the role of Toll-like receptor 2 (TLR2) and TLR9 in HIV-long terminal repeat (HIV-LTR) trans-activation and assessed whether TLR4 synergized with TLR2 or TLR9 to induce HIV replication. Soluble Mycobacterium tuberculosis factor (STF) and phenol-soluble modulin from Staphylococcus epidermidis induced HIV-LTR trans-activation in human microvessel endothelial cells cotransfected with TLR2 cDNA. Stimulation of ex vivo spleen cells from HIV-1 transgenic mice with TLR4, TLR2, and TLR9 ligands (LPS, STF, and CpG DNA, respectively) induced p24 Ag production in a dose-dependent manner. Costimulation of HIV-1 transgenic mice spleen cells with LPS and STF or CpG DNA induced TNF-α and IFN-γ production in a synergistic manner and p24 production in an additive fashion. In the THP-1 human monocytic cell line stably expressing the HIV-LTR-luciferase construct, LPS and STF also induced HIV-LTR trans-activation in an additive manner. This is the first time that TLR2 and TLR9 and costimulation of TLRs have been shown to induce HIV replication. Together these results underscore the importance of TLRs in bacterial Ag- and CpG DNA-induced HIV-LTR trans-activation and HIV replication. These observations may be important in understanding the role of the innate immune system and the molecular mechanisms involved in the increased HIV replication and HIV disease progression associated with multiple opportunistic infections.

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal RepeatTrans-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Equils

Schito

Karahashi

et al. 2003

The Journal of Immunology

100

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“…Nucleic acid vaccination has been achieved in experimental models of invasive fungal disease due to C. immitis, P. brasiliensis, A. fumigatus and P. marneffei 91,93,[109][110][111][112][113][114][115][116][117] . Most studies so far have examined C. immitis antigens, especially Ag2/PRA, the expression library immunization-antigen 1 (ELI-Ag1) and urease 3,118 .…”

Section: Stimulating Multiple Arms Of Immunitymentioning

confidence: 99%

Advances in combating fungal diseases: vaccines on the threshold

2006

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The dramatic increase in fungal diseases in recent years can be attributed to the increased aggressiveness of medical therapy and other human activities. Immunosuppressed patients are at risk of contracting fungal diseases in healthcare settings and from natural environments. Increased prescribing of antifungals has led to the emergence of resistant fungi, resulting in treatment challenges. These concerns, together with the elucidation of the mechanisms of protective immunity against fungal diseases, have renewed interest in the development of vaccines against the mycoses. Most research has used murine models of human disease and, as we review in this article, the knowledge gained from these studies has advanced to the point where the development of vaccines targeting human fungal pathogens is now a realistic and achievable goal.For many years, the concept of developing vaccines against fungal diseases attracted little interest, but this has changed in the past fifteen years (reviewed in REFS 1-6 ) because of the dramatic increase in the incidence rates of fungal diseases worldwide. Carbohydrate and, especially, protein antigens that exert protective immunity against various fungal diseases have now been identified. Fungal carbohydrates can induce the production of antibodies that enhance host resistance in many ways and, fuelled by advances in cellular and molecular biology, numerous fungal proteins that trigger T-cell-mediated immunity and that are immunogenic in murine models of fungal disease have been identified (TABLE 1). A vaccine based on one or more of these candidate antigens could prevent disease by inducing protective antibodies, T-cell-mediated immunity or a combination of both of these aspects of the host immune response. In this Review, we will assess the state of fungal vaccine development, both prophylactic and therapeutic. Overview of the immune response to fungiSuccessful resolution of the diseases caused by pathogenic fungi is crucially dependent on the coordinated interactions of many constituents of the host immune response. The host response to these organisms varies, as would be expected for such a heterogeneous group of pathogens, which differ morphologically, genetically and biochemically. Therefore, the effector molecules and cells that are important for combating opportunistic fungi such as Candida and Aspergillus spp. are less important for primary pathogens such as Coccidioides spp. and Histoplasma capsulatum (BOX 1). The innate response to fungiAs with all pathogens, the innate immune system is a crucial determinant in the antifungal response (FIG. 1) The non-cellular effectors of innate immunity comprise collectins, complement and natural antibodies. These molecules mediate opsonization and therefore promote the ingestion of fungi by phagocytes. One member of the collectin family, pentraxin 3, is necessary for the response to Aspergillus spp. 23 , and the pulmonary collectins surfactant proteins A and D not only cause aggregation of fungi but also have fungicidal activity ...

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“…In particular, naked-DNA vaccination has arisen as an effective strategy in the preventive medicine field with promising future prospects. The ability of pDNA to activate both the humoral and cellular immune systems against the encoded antigen (Liu 2003; Manthorpe et al 2005;McDonnell and Askari 1996;Weide et al 2008) have resulted in an intensive study of new strategies aimed at increasing the DNA vaccine immunogenicity.…”

Section: The Relevance Of Pdna On Emerging Gene Therapiesmentioning

confidence: 99%

Biomedical application of plasmid DNA in gene therapy: A new challenge for chromatography

Sousa

Passarinha²,

Queiroz³

2009

Biotechnology and Genetic Engineering Reviews

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Gene therapy and DNA vaccination are clinical fields gradually emerging in the last few decades, in particular after the discovery of some gene-related diseases. The increased relevance of biomedical applications of plasmid DNA (pDNA) to induce therapeutic effects has had a great impact on biopharmaceutical research and industry. Although there are several steps involved in the pDNA manufacturing process, the several unit operations must be designed and integrated into a global process. After the plasmid has been designed according to the requirements for clinical administeration to humans, it is biosynthesised mainly by an E. coli host. The overriding priority of the production process is to improve plasmid quantity -the production conditions need to be optimised to guarantee pDNA stability and biological activity.The complexity and diversity of biomolecules present on the pDNA-containing extracts represent the main concern and limitation to achieve pure and biologically active pDNA. There has been a recent intenstification of the improvement of existing purification procedures or the establishment of novel schemes for plasmid purification.

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DNA Vaccines

Cited by 155 publications

References 0 publications

Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal RepeatTrans-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Toll-Like Receptor 2 (TLR2) and TLR9 Signaling Results in HIV-Long Terminal RepeatTrans-Activation and HIV Replication in HIV-1 Transgenic Mouse Spleen Cells: Implications of Simultaneous Activation of TLRs on HIV Replication

Advances in combating fungal diseases: vaccines on the threshold

Biomedical application of plasmid DNA in gene therapy: A new challenge for chromatography

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