Abstract
Cervical cancer is a common type of cancer among women worldwide and infection with high-risk human papillomavirus (HPVs) types represents the major risk factor for the etiopathogenesis of the disease. HPV-16 is the most frequently identified HPV type in cervical lesions and expression of E6 and E7 oncoproteins is required for the uncontrolled cellular proliferation. In the present study we report the design and experimental testing of a recombinant multi-epitope protein containing immunogenic epitopes of HPV-16 E6 and E7. Tumor preventive assays, based on the engraftment of TC-1 cells in mice, showed that the E6E7 multi-epitope protein induced a full preventive anti-tumor protection in wild-type mice, as well as in mice deficient in expression of CD4+ T cells and TLR4 receptor. Nonetheless, no anti-tumor protection was observed in mice deficient in CD8+ T cells. Also, the vaccine promoted high activation of E6/E7-specific T cells and in a therapeutic-approach, E6E7 protein conferred full anti-tumor protection in mice. These results show a potential use of this E6E7 multi-epitope antigen as a new and promising antigen for the development of a therapeutic vaccine against tumors induced by HPV.
Highlights
Cervical cancer is the fourth most common type of cancer among women worldwide [1]
As an attempt to reduce the high incidence of this infection and the deaths resulting from cervical cancer, as well as other cancer types induced by human papillomavirus (HPVs), two prophylactic vaccines based on L1 antigen have been approved in more than 100 countries
The E6E7 antigen was designed to contain HPV E6 and E7 immunogenic epitopes based on published data reporting antigen specific cellular immune responses detected in patients and/ or C57BL/6 mice
Summary
Cervical cancer is the fourth most common type of cancer among women worldwide [1]. Persistent infection with high-risk human papillomavirus (HPVs) is the primary risk factor for the development of the disease. As an attempt to reduce the high incidence of this infection and the deaths resulting from cervical cancer, as well as other cancer types induced by HPV, two prophylactic vaccines based on L1 antigen have been approved in more than 100 countries. Both vaccines have proven to be highly effective in preventing HPV infection, neither one shows therapeutic effects to established HPV infections. PLOS ONE | DOI:10.1371/journal.pone.0138686 September 21, 2015
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