Comparing the effect of molecular and biological adjuvant on the efficiency of HPV-16 based DNA vaccines in cervical cancer model

Cervical cancer is one of the most common cancer in women worldwide. This cancer is highly associated with the most common sexually transmitted infection, most often whit high-risk human papillomavirus (HPV) HPV16 and HPV18. The infections causing lesions can lead to benign (wart, papillomas, condylomas) and the malignancies such as cervix, anus, penis, and head and neck cancer. DNA vaccines are attractive tools for the development of HPV vaccines and inducing antigen-specific immunity. But, there is a need to increase their potency by using suitable adjuvants However, DNA vaccine alone have limited immunogenicity and therefore, appropriate strategies are needed for increasing their potency such as using an adjuvant. In this study, we used two HPV-16 therapeutic DNA vaccines, pcDNA-E7 and pcDNAL1, assisted with HSP70 or Brucella abortus RB51 lipopolysaccharide (LPS) as an adjuvant. The aim of this study was the comparison of the efficacy of candidate adjuvants along with two DNA vaccines, pcDNA-E7 and pcDNA-L1, in induction of CTL responses Methods In this study, TC-1 cells were injected subcutaneously to the back of C57BL/6 mice in a volume of 100 μl. For DNA vaccine immunizations, mice were immunized intradermally with a total of 50 μg HPV DNA vaccine containing HPV-16 E7 and HPV-16 L1 DNA alone, or along with adjuvant. To determine T-cell immune responses, different cytokines such as IFN-γ and IL-4 were evaluated Mice were immunized with the plasmid DNA after pre-treatment with cardiotoxin. The splenocytes of immunized mice were then tested for CTL activity by detecting the cytokine production by ELISA, and lymphocyte stimulation by MTT assay. Based on the results immunization with pcDNA-E7 or pcDNA-L1 alone could induce strong cellular immune responses, but comparative assessments of these vaccines show that co-administration of HPV-16 E7 and HPV-16 L1 DNA vaccines assisted with R-LPS or HSP70 induced a stronger antigen-specific cellular immune responses and protect mice against TC-1 tumor cell challenges The administration of B.abortus RB51 LPS (R-LPS) or HSP70 along with E7&L1 gene plasmid induced HPV16-specific cellular immune responses and protect against TC-1 induced tumor in vivo. We showed that this vaccine was immunogenic, and protective in the TC-1 tumor model. Furthermore, B.abortus RB51 LPS (R-LPS) may be an adequate alternative to HSP70 for enhancing of therapeutic effect of DNA vaccines. However, to improve the immunogenicity polytope based DNA vaccines which elicit multiple effector and memory CTL responses should be considered in future studies of DNA-based cancer vaccines

کلیدواژه ها:

DNA Vaccine ، E7 ، L1 ، adjvant ، Human Papillomavirus Type 16