Human papillomavirus (HPV) a non-enveloped virus accounted as the most important causative agent of cervical cancer worldwide with more than 45,000 diagnosed cases annually (1). Even after establishment of encouraging vaccine platforms for it,s prevention due to shortages of this supplements the infection rate remained accelerating in developing country. Yet, more than 100 types of HPV distinguished by genetic analysis among them types 16 and 18 belonged to definite carcinogens group are responsible for more than 62% and 15% of cervical cancers respectively(2, 3). The major limitation associated with current HPV available vaccines is their useless application for therapeutic approaches indeed so developing a suitable therapeutic vaccine remained a big challenge in this era (4) .
In persistent infection like HPV related diseases, therapeutic vaccine open a new horizon for better control of disease by improving the cellular immune arm against virus proteins expressed in host cells (5). Among different therapeutic vaccine strategies including virus based vectors, peptide vaccine, whole bacterial vectors, recombinant DNA vaccine, protein based vaccine has its special situation in HPV related diseases therapy. Protein-based vaccines are capable of generating CD8+ T-cell responses either on humoral immune response in vaccinated animals (6). Also while this kind of vaccines is safer compared to bacterial/viral and circumvent MHC restriction in spite of peptide vaccines however has some shortages most importantly poor immunogenicity when compared to others (2). Thus, novel HPV protein-based vaccines require new strategies for promotion of consequent CD8+ and humoral related immune responses to combat disease progression.
Up to now several therapeutic vaccine candidates that target HPV E6 and/or E7 proteins have been explored in animals and human being (2, 6). These oncoproteins that play crucial roles during disease progression expressed permanently in almost all infected cells and has a significant degree of conservatism among different genotypes so accepted as suitable target antigens for vaccine therapy purposes(7). Albeit it must be keep in mind that before examine of E7 protein as a vaccine antigen its oncogenesity should be overwhelmed by some point mutations. This oncogenic-sterile protein designated as E7 detox (E7d) employed in some experiments with sustained achievements so far and entered into phase I clinical trial in the form of E7(detox)/HSP70 fusion DNA vaccine (http://clinicaltrials.gov/show/NCT00121173) (8).
Numerous strategies to increase potency of these protein-based vaccines have been studied among them employment of wide spectrum of adjuvants in mix formulation or in fusion form with antigen has considerable position (2, 9). Among well characterized adjuvant Toll-like receptor agonists due to engaging TLR compartment during triggering the immune response has attractive properties(9, 10). It is demonstrated that signaling through...