Journal
VACCINE
Volume 28, Issue 44, Pages 7146-7154Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.08.070
Keywords
T-cells; Dendritic cells; Vaccination; Peptides; Antigen targeting
Categories
Funding
- Ministerio de Educacion y Ciencia (MEC) [SAF2007-61432]
- Gobierno de Navarra
- UTE
- Ligue Nationale Contre le Cancer
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Staphylococcus epidermidis releases a complex of at least four peptides, termed phenol-soluble modulins (PSM), which stimulate macrophages to produce proinflammatory cytokines via activation of TLR2 signalling pathway. We demonstrated that covalent linkage of PSM peptides to an antigen facilitate its capture by dendritic cells and, in combination with different TLR ligands, can favour the in vivo induction of strong and persistent antigen-specific immune responses. Treatment of mice grafted with HPV16-E7-expressing tumor cells (TC-1)with poly(l: C) and a peptide containing alpha Mod linked to the H-2D(b)-restricted cytotoxic T-cell epitope E7(49-57) from HPV16-E7 protein allowed complete tumor regression in 100% of the animals. Surprisingly, this immunomodulatory property of modulin-derived peptides was TLR2 independent and partially dependent upon the EGF-receptor signalling pathway. Our results suggest that alpha or gamma modulin peptides may serve as a suitable antigen carrier for the development of anti-tumoral or anti-viral vaccines. (C) 2010 Elsevier Ltd. All rights reserved.
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