Can we vaccinate against Type 1 diabetes?

Article (PDF Available)inF1000 Biology Reports 4(1):19 · October 2012with12 Reads
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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    • "An extension to this pillar is ASI which enables the body to establish immune regulation using natural immune regulatory networks. In some embodiments, ASI exploits systemic injection of autoimmunogenic epitopes/antigens without co-stimulation to generate default regulatory responses [26,27,122]. It remains unclear whether this is achieved via de novo generation of Tregs or trans-differentation/conversion of effector T cells [123,124]. "
    [Show abstract] [Hide abstract] ABSTRACT: Type 1 diabetes was one of the earliest disorders to be associated with the phenomenon of autoimmunity and is one of the most studied organ-specific autoimmune diseases at the epidemiologic, immunologic and genetic level. Despite this, and the emergence of a plethora of strategies for trying to intervene in, or prevent the disease, it remains at some distance from being reliably and safely tractable by immunotherapy, a source of great frustration in this research field. In this article we review some of the key concepts that might impact upon this lack of success in the clinic going forward. These include new insights into autoreactive CD4 and CD8 T cell biology and a discussion of the concept of disease heterogeneity as it applies to type 1 diabetes. The onset of disease is characterised by a delicate equilibrium of proinflammatory and regulatory T cells, which we have termed "balanced autoreactive set-point", and which may be amenable to antigen-specific immunotherapies that alter the rate of disease progression. Advances in the characterization of T cells, especially at the single cell level, could be rewarding, notably from the vantage point of biomarker and surrogate discovery. A better understanding of T cell targeting, autoantigen processing and the β-cell:immune interface is also needed, although access to diseased tissues is a major limitation in this effort. Finally, the existence of disease heterogeneity is an emerging theme in this and other complex immunopathologies, and could be both a blessing (finding the right drug for the right person) and a hindrance (compromising the power of early-stage trials of emerging therapeutics).
    Full-text · Article · Sep 2015
  • [Show abstract] [Hide abstract] 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.
    Article · Sep 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Tiago Morais, Sara Andrade, Sofia S Pereira, Mariana P MonteiroDepartment of Anatomy, Unit for Multidisciplinary Biomedical Research, Institute for Biomedical Sciences Abel Salazar, University of Porto, Porto, PortugalAbstract: Several metabolic disorders, such as diabetes, hypertension, dyslipidemia, and obesity, represent significant risk factors for cardiovascular disease, which is the leading cause of morbidity and mortality among adult populations in western societies. Understandably, these chronic disorders have now replaced infectious diseases as the most important public health problem and economic burden to society in most countries. Treatment of metabolic risk factors in order to prevent cardiovascular disease requires an enduring approach with multiple drugs, which can be associated with considerable costs, side effects, and a low rate of therapeutic compliance due to lack of symptoms until later stages of the disease. Since vaccines have proven to be a powerful and effective approach to preventing infectious diseases, attempts to expand the therapeutic use of vaccines into the context of highly prevalent diseases has been attracting increased research interest. Vaccination strategies for chronic diseases in particular are an exciting area of research, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing on the use of molecular vaccines for the treatment of common and highly prevalent chronic metabolic disorders, ie, diabetes, hypertension, dyslipidemia, and obesity.Keywords: vaccines, diabetes, hypertension, dyslipidemia, obesity
    Full-text · Article · Sep 2014

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