Recombinant Leishmania tarentolae encoding the HPV type 16 E7 gene in tumor mice model. (November 2012)

• Record Type: Journal Article
• Authors: Salehi, Maryam; Taheri, Tahereh; Mohit, Elham; Zahedifard, Farnaz; Seyed, Negar; Taslimi, Yasaman; Sattari, Mandana; Bolhassani, Azam; Rafati, Sima
• Is Part Of: Immunotherapy. Volume 4:Number 11(2012:Nov.)
• Page Start: 1107
• Page End: 1120
• Publication Date: 2012-11
• Subjects: E7 -- HPV -- Leishmania tarentolae -- live vaccine -- TC-1 -- tumor; Immunotherapy -- Periodicals; 615.37
• DOI: 10.2217/imt.12.110
• Languages: English
• ISSNs: 1750-743X

Abstract

Background: Cervical cancer, the third most prevalent cause of cancer in women worldwide, is associated with HPVs. The critical role of E7 protein in HPV-related malignancies has designated it as a strong contender for generating vaccines against HPV.Materials & methods: In this study, we developed a novel live vaccine using recombinant Leishmania tarentolae expressing E7-green fluorescent protein (GFP) fusion protein for the protection of mice against HPV-associated tumors. In order to transfect L. tarentolae with E7-GFP fusion construct, pLEXSY-neo2 system was applied. Followed by PCR, fluorescence imaging and fluorescence-activated cell sorting analysis, integration of E7-GFP gene into parasites genome was confirmed. A comparative study of six groups of C57BL/6 mice was performed to analyze antigen-specific humoral and cellular immune responses against E7 encoding live and DNA vaccines. Furthermore, the anti-tumor protective effect of L. tarentolae -E7-GFP was compared to other vaccination strategies, namely pcDNA-E7 as the DNA vaccine and pcDNA-E7/ L. tarentolae -E7-GFP as the prime-boost regimen.Results: We found that E7-GFP expressing recombinant L. tarentolae induces significant levels of IgG2a and IFN-γ, while there is no significant IL-5 production compared with that of other strategies and control groups before and after challenge with TC-1 tumor cells. It is noteworthy that the designed live vaccine showed the best protection and minimum tumor size among all groups against TC-1-induced tumors.Conclusion: Overall, the results obtained revealed that the E7-GFP recombinant L. tarentolae could be a potential live vaccine for induction of immune responses in vivo .