Journal
NATURE CHEMICAL BIOLOGY
Volume 10, Issue 11, Pages 943-949Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.1640
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Funding
- New Zealand Ministry of Science and Innovation [C08X0808]
- research grant from the New Zealand Health Research Council
- Rotary Club of Wellington
- University of Otago
- US National Institutes of Health Tetramer Core Facility [HHSN272201300006C]
- New Zealand Ministry of Business, Innovation & Employment (MBIE) [C08X0808] Funding Source: New Zealand Ministry of Business, Innovation & Employment (MBIE)
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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 pro-drug of the natural killer-like T (NKT) cell agonist a-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.
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