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Can we vaccinate against Type 1 diabetes?

Department of Immunobiology, King's College London and National Institute for Health Research Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London 2nd Floor, Borough Wing, Guy's Hospital, London, SE1 9RT UK.
F1000 Biology Reports 10/2012; 4:19. DOI: 10.3410/B4-19
Source: PubMed

ABSTRACT Vaccination is the administration of antigenic material to stimulate the immune system to develop adaptive immunity to a disease. As the most successful prophylactic in medical history, there is now an emerging interest as to whether vaccination can be applied in autoimmune and inflammatory conditions. These are diseases of failed immune regulation; vaccination in this context aims to exploit the power of antigenic material to stimulate immune homeostasis in the form of active, adaptive, regulatory immune responses. Type 1 diabetes is an autoimmune disease that could benefit from the therapeutic potential of vaccination. The major conditions necessary to make prophylaxis feasible are in place; the self antigens are known, the failure of existing immune regulation has been demonstrated, early studies of vaccine approaches have proved safe, and the preclinical prodrome of the disease can be easily detected by simple blood tests. Challenges for future implementation include finding the best mode of delivery and the best blend of adjunctive therapies that create the favorable conditions required for a vaccine to be effective.

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    ABSTRACT: Some clinical trials in humans have aimed at modulation of type 1 diabetes (T1D) via alteration of the immune response to putative islet cell antigens, particularly proinsulin and insulin, glutamic acid decarboxylase and the peptide, DiaPep 277, derived from heat shock protein 60. The focus here is on development of a specially engineered DNA plasmid encoding proinsulin to treat T1D. The plasmid is engineered to turn off adaptive immunity to proinsulin. This approach yielded exciting results in a randomized placebo controlled trial in 80 adult patients with T1D (1). The implications of this trial are explored in regards to the potential for sparing inflammation in islets and thus allowing the functioning beta cells to recover and produce more insulin. Strategies to further strengthen the effects seen thus far with the tolerizing DNA plasmid to proinsulin will be elucidated. The DNA platform affords an opportunity for easy modifications. In addition standard exploration of dose levels, route of administration and frequency of dose are practical. Optimization of the effects seen to date on C-peptide and on depletion of proinsulin specific CD8 T cells are feasible, with expected concomitant improvement in other parameters like hemoglobin A1c and reduction in insulin usage. T1D is one of the few autoimmune conditions where antigen specific therapy can be achieved, provided the approach is tested intelligently. Tolerizing DNA vaccines to proinsulin and other islet cell autoantigens is a worthy pursuit to potentially treat, prevent and to perhaps even 'cure' or 'prevent' type 1 diabetes.
    Clinical Immunology 09/2013; DOI:10.1016/j.clim.2013.08.010 · 3.77 Impact Factor

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