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Immunotherapy. 2012 Nov;4(11):1107-20. doi: 10.2217/imt.12.110.

Recombinant Leishmania tarentolae encoding the HPV type 16 E7 gene in tumor mice model.

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  • 1Molecular Immunology & Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran.

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.

PMID:
23194361
[PubMed - indexed for MEDLINE]
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