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  • 1
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Immunological reviews 179 (2001), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses which characterize allergic diseases, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities which mediate allergic reactions, and traditional protein-based allergen IT has a limited scope of efficacy. However, a number of reagents collectively termed DNA-based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2-mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA-based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen–ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. Results from many laboratories have generated guarded optimism that DNA-based immunotherapeutics may be effective for the reversal of allergic hypersensitivity states in humans, and several clinical trials have already been initiated. This review will focus on our present understanding of the biological activities of DNA-based immunotherapeutics and their application to the treatment of allergic diseases.This work was supported by grants AI40682 and AI01490 from the NIH and by a grant from Dynavax Technologies Corporation. J.H.V. is also a Medical Scientist Training Program Trainee.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Immunological reviews 199 (2004), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary:  Conjugation of protein antigen with immunostimulatory oligonucleotides creates a potent immunogen. Physical linking of oligonucleotides to antigen enhances antigen uptake and targets the adjuvant properties of the oligonucleotides to the antigen-presenting cell. In addition, the conjugated oligonucleotides appear to have improved immunostimulatory abilities compared to free oligonucleotides, presumably due to enhanced activation of Toll-like receptor 9. Immunization with these conjugate preparations elicits antigen-specific antibody responses, a T-helper cell 1-biased cytokine profile from CD4 T cells, and CD8 cytotoxic T-lymphocyte activity that is CD4 independent. The humoral and cellular immune responses induced by these conjugates suggest they can be used to create effective vaccines against infectious pathogens and tumors and to beneficially modulate allergic responses. Indeed, recent clinical trial data show symptom relief and immunomodulation of the allergic response in patients with allergic rhinitis. This review considers the mechanisms of action of antigen–oligonucleotide conjugates and discusses available data regarding their use for the prevention and treatment of infectious, oncologic, and allergic diseases.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: At present, avoidance is the only therapeutic option available for individuals with food allergies. However, studies suggest that DNA-based vaccination might be an effective therapeutic option for the reversal of allergic hypersensitivities, including allergies to foods. Because severe anaphylactic reactions represent a life-threatening risk for individuals with food allergies, we and others have evaluated the effectiveness of DNA-based vaccination for the prevention of anaphylactic hypersensitivity in murine models. Our investigations demonstrated that primary gene and protein/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) vaccination of subsequently Th2-sensitized mice reduced the risk of death after anaphylactic challenge, significantly. In addition, gene and protein/ISS-ODN vaccination reduced post challenge plasma histamine levels. Analysis of the immune profiles of mice receiving DNA-based vaccines showed that both gene and protein/ISS-ODN vaccination effectively prevented the development of Th2-biased immune profiles after sensitization. In contrast, vaccination with protein alone, the experimental equivalent of the traditional protein-based immunotherapy (IT) reagents used in clinical practice provided no protection from anaphylaxis, nor did it prevent the development of a Th2-biased immune profile after allergen sensitization. These studies justify continued optimism in the potential of DNA-based vaccination for the desensitization of food allergic individuals.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Springer seminars in immunopathology 22 (2000), S. 133-146 
    ISSN: 1432-2196
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Springer seminars in immunopathology 22 (2000), S. 85-96 
    ISSN: 1432-2196
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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