Clin Exp Vaccine Res.  2013 Jul;2(2):128-134. 10.7774/cevr.2013.2.2.128.

Intranasal immunization with a flagellin-adjuvanted peptide anticancer vaccine prevents tumor development by enhancing specific cytotoxic T lymphocyte response in a mouse model

Affiliations
  • 1Clinical Vaccine R&D Center, Chonnam National University, Gwangju, Korea. selee@chonnam.ac.kr
  • 2Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Korea.
  • 3Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea.

Abstract

PURPOSE
Human papillomavirus (HPV) is a significant cause of cervical cancer-related deaths worldwide. Because HPV is a sexually transmitted mucosal pathogen, enhancement of antigen-specific mucosal immune response likely serves good strategy for vaccination. However, mucosal vaccines generally do not induce strong enough immune responses. Previously we proved that a bacterial flagellin, Vibrio vulnificus FlaB, induce strong antigen-specific immune responses by stimulating the Toll-like receptor 5. In this study, we tested whether FlaB could serve as an effective mucosal adjuvant for a peptide-based HPV preventive cancer vaccine.
MATERIALS AND METHODS
Mice were intranasally administered with a mixture of FlaB and E6/E7 protective peptides in 5-day interval for a total of two times. Five-days after the last vaccination, cellular immune responses of the vaccinated mice were analyzed. Tumor growth was also observed after a subcutaneous implantation of TC-1 cells bearing E6/E7 antigens.
RESULTS
Intranasal administration of the E6/E7 peptide mixture with FlaB elicited a strong antigen-specific cytotoxic T lymphocyte activity and antigen-specific interferon-gamma production from splenocytes and cervical lymph node cells. Furthermore, FlaB, as a mucosal adjuvant, conferred an excellent protection against TC-1 tumor challenge with high survival rates in E6/E7 immunized animals.
CONCLUSION
These results indicate that FlaB can be a promising mucosal adjuvant for nasal HPV vaccine development.

Keyword

Flagellin; Adjuvant; Neoplasms; Vaccines

MeSH Terms

Administration, Intranasal
Animals
Flagellin
Humans
Immunity, Cellular
Immunity, Mucosal
Immunization
Interferon-gamma
Lymph Nodes
Lymphocytes
Mice
Peptides
Survival Rate
Toll-Like Receptor 5
Ursidae
Vaccination
Vaccines
Vibrio vulnificus
Flagellin
Interferon-gamma
Peptides
Toll-Like Receptor 5
Vaccines
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