Induction of human papillomavirus oncogene-specific CD8 T-cell effector responses in the genital mucosa of vaccinated mice.

Details

Serval ID
serval:BIB_C8FA50D44220
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Induction of human papillomavirus oncogene-specific CD8 T-cell effector responses in the genital mucosa of vaccinated mice.
Journal
International Journal of Cancer
Author(s)
Decrausaz L., Revaz V., Bobst M., Corthésy B., Romero P., Nardelli-Haefliger D.
ISSN
1097-0215[electronic], 0020-7136[linking]
Publication state
Published
Issued date
2010
Volume
126
Number
10
Pages
2469-2478
Language
english
Abstract
Cervical cancer, the second leading cause of cancer mortality in women worldwide, results from infection with a subset of human papillomaviruses (HPV), HPV-16 being the most prevalent type. The available prophylactic vaccines are an effective strategy to prevent this cancer in the long term. However, they only target 70-80% of all cervical cancers and cannot control existing HPV infections and associated lesions. Therapeutic vaccines are thus necessary for women who cannot benefit from prophylactic vaccination. Induction of protective immune responses in the genital mucosa (GM) may be crucial for efficacy of HPV therapeutic vaccines. We report here that mice that received a single subcutaneous (s.c.) vaccination of an adjuvanted long synthetic HPV16 E7(1-98) polypeptide showed induction of 100% tumor protection against s.c. TC-1 tumors and that tumor regression was mainly provided by CD8 T cells. In vivo cytotoxic assay revealed high E7-specific cytolytic T lymphocytes activity in spleen and in genital draining lymph nodes (LN), and E7-specific CD8 T cells could be detected in GM by tetramer staining. More importantly, high-avidity E7-specific INF-gamma secreting CD8 T cells were induced not only in blood, spleen and LN but also in GM of vaccinated mice, thus providing evidence that a parenteral vaccination may be sufficient to provide regression of genital tumors. In addition, there was no correlation between the responses measured in blood with those measured in GM, highlighting the necessity and relevance to determine the immune responses in the mucosa where HPV-tumors reside.
Keywords
Alphapapillomavirus/immunology, Animals, CD8-Positive T-Lymphocytes/immunology, Female, Genitalia, Female/immunology, Interferon-gamma/immunology, Mice, Mice, Inbred C57BL, Mucous Membrane/immunology, Papillomavirus E7 Proteins/immunology, Papillomavirus Infections/complications, Papillomavirus Infections/drug therapy, Papillomavirus Vaccines/administration & dosage, Tumor Virus Infections/complications, Tumor Virus Infections/drug therapy, Uterine Cervical Neoplasms/drug therapy, Uterine Cervical Neoplasms/immunology
Pubmed
Web of science
Open Access
Yes
Create date
24/06/2010 17:55
Last modification date
20/08/2019 16:44
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