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Nat Chem Biol. 2014 Nov;10(11):943-9. doi: 10.1038/nchembio.1640. Epub 2014 Oct 5.

A self-adjuvanting vaccine induces cytotoxic T lymphocytes that suppress allergy.

Author information

1
The Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
2
Malaghan Institute of Medical Research, Wellington, New Zealand.
3
1] Malaghan Institute of Medical Research, Wellington, New Zealand. [2] Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, Wellington, New Zealand.
4
Capital and Coast District Health Board, Wellington, New Zealand.
5
Department of Chemistry, University of Otago, Dunedin, New Zealand.
6
1] Malaghan Institute of Medical Research, Wellington, New Zealand. [2] School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.

Abstract

Epitope-based peptide vaccines encompass minimal immunogenic regions of protein antigens to allow stimulation of precisely targeted adaptive immune responses. However, because efficacy is largely determined by the functional status of antigen-presenting cells (APCs) that acquire and present peptides to cells of the adaptive immune system, adjuvant compounds are needed to enhance immunogenicity. We present here a vaccine consisting of an allergen-derived peptide conjugated to a prodrug of the natural killer-like T (NKT) cell agonist α-galactosylceramide, which is highly effective in reducing inflammation in a mouse model of allergic airway inflammation. Unlike other peptide-adjuvant conjugates that directly activate APCs through pattern recognition pathways, this vaccine encourages third-party interactions with NKT cells to enhance APC function. Therapeutic efficacy was correlated with marked increases in the number and functional activity of allergen-specific cytotoxic T lymphocytes (CTLs), leading to suppression of immune infiltration into the lungs after allergen challenge in sensitized hosts.

PMID:
25282504
DOI:
10.1038/nchembio.1640
[Indexed for MEDLINE]

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