REVIEW ARTICLE
Front. Immunol., 20 August 2013 | doi: 10.3389/fimmu.2013.00245
Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases
- Immunology, Infectious Diseases and Immunology, Faculty Veterinary Medicine, University Utrecht, Utrecht, Netherlands
Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation and the observed side effects of these therapies illustrate the pressing need for more specific interventions. Regulatory T-cells (Treg) are pivotal controllers of (auto-aggressive) immune responses and inflammation, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Therefore, Treg became frequently studied targets for more specific immunotherapy. Especially antigen-specific targeting of Treg would enable local and tailor made interventions, while obviating the negative side effect of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for antigen-specific interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory-site. In this perspective heat shock proteins (Hsp) have several characteristics that make them highly attractive targets for antigen-specific Treg inducing therapy. The development of an antigen-specific Treg inducing vaccine is a major novel goal in the field of immunotherapy in autoimmune diseases. However, progress is hampered not only by the lack of effective antigens, but also by the fact that other factors such as dose, route, and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to the effective induction of Treg. In addition, the use of a Treg inducing adjuvant might be required to achieve an effective regulatory response, in the case of ongoing inflammation. Future goals in clinical trials will be the optimization of natural Treg expansion (or the induction of adaptive Treg) without loss of their suppressive function or the concomitant induction of non-regulatory T-cells. Here, we will discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic inflammatory conditions.
Keywords: regulatory T-cells, immunologic adjuvants, therapeutic vaccines, Treg inducing adjuvants, autoimmunity
Citation: Keijzer C, Zee Rvd, Eden Wv and Broere F (2013) Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases. Front. Immunol. 4:245. doi: 10.3389/fimmu.2013.00245
Received: 09 June 2013; Paper pending published: 12 July 2013;
Accepted: 06 August 2013; Published online: 20 August 2013.
Accepted: 06 August 2013; Published online: 20 August 2013.
Edited by:
Virgil Schijns, Wageningen University, Netherlands
Reviewed by:
Urszula Krzych, Walter Reed Army Institute of Research, USAPaola Massari, Boston University, USA
Copyright: © 2013 Keijzer, Zee, Eden and Broere. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Femke Broere, Immunology, Infectious Diseases and Immunology, University Utrecht, Faculty Veterinary Medicine Yalelaan 1, Utrecht 3584CL, Netherlands e-mail: f.broere@uu.nl
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