Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human papillomavirus-associated genital-tumor regression in mice.

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Version: Final published version
Serval ID
serval:BIB_688E4F5E989B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human papillomavirus-associated genital-tumor regression in mice.
Journal
Mucosal Immunology
Author(s)
Domingos-Pereira S., Decrausaz L., Derré L., Bobst M., Romero P., Schiller J.T., Jichlinski P., Nardelli-Haefliger D.
ISSN
1935-3456 (Electronic)
ISSN-L
1933-0219
Publication state
Published
Issued date
2012
Volume
6
Number
2
Pages
393-404
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
Human papillomaviruses (HPV)-related cervical cancer is the second leading cause of cancer death in women worldwide. Despite active development, HPV E6/E7 oncogene-specific therapeutic vaccines have had limited clinical efficacy to date. Here, we report that intravaginal (IVAG) instillation of CpG-ODN (TLR9 agonist) or poly-(I:C) (TLR3 agonist) after subcutaneous E7 vaccination increased ∼fivefold the number of vaccine-specific interferon-γ-secreting CD8 T cells in the genital mucosa (GM) of mice, without affecting the E7-specific systemic response. The IVAG treatment locally increased both E7-specific and total CD8 T cells, but not CD4 T cells. This previously unreported selective recruitment of CD8 T cells from the periphery by IVAG CpG-ODN or poly-(I:C) was mediated by TLR9 and TLR3/melanoma differentiation-associated gene 5 signaling pathways, respectively. For CpG, this recruitment was associated with a higher proportion of GM-localized CD8 T cells expressing both CCR5 and CXCR3 chemokine receptors and E-selectin ligands. Most interestingly, IVAG CpG-ODN following vaccination led to complete regression of large genital HPV tumors in 75% of mice, instead of 20% with vaccination alone. These findings suggest that mucosal application of immunostimulatory molecules might substantially increase the effectiveness of parenterally administered vaccines.Mucosal Immunology advance online publication 12 September 2012; doi:10.1038/mi.2012.83.
Pubmed
Web of science
Open Access
Yes
Create date
03/09/2011 19:52
Last modification date
20/08/2019 14:23
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