Prevention and treatment of cervical cancer by a single administration of human papillomavirus peptide vaccine with CpG oligodeoxynucleotides as an adjuvant in vivo.

No licensed therapeutic human papillomavirus (HPV) vaccine is currently available, so it remains a high priority to develop a therapeutic HPV vaccine or prophylactic/therapeutic HPV vaccine for cervical cancer. In this current study, we designed an HPV vaccine including CpG oligodeoxynucleotides 1826 as an adjuvant and HPV16 E7 43-77 peptide as antigen, which contains a CD8 T cell epitope (E7 49-57), and two CD4 T cell epitopes (E7 43-77 and E7 50-62). The prophylactic and therapeutic effect on cervical cancer induced by a single administration of vaccine, were comprehensively evaluated by examining the tumor size and the percentage of tumor-free/bearing mice. The cellular immunity and modulation of immunosuppressive cells induced by the vaccine were evaluated by examining intracellular cytokine staining (ICS) of splenocytes and FCM, respectively. Antigen-specific cytotoxic T-lymphocyte (CTL) responses were investigated using in vivo cytolytic assay. The results showed that the single administration of vaccine elicited significant prophylactic as well as therapeutic effect on cervical cancer. The increased cellular immunity mediated by CD4 + IFN-γ + T cells and CD8 + IFN-γ + T cells, and the decreased numbers of immunosuppressive cells including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were induced by the vaccine. Antigen-specific CTL response was also induced by vaccination. These findings suggested that significant anti-tumor effect of the vaccine may result from the induction of increased cellular immunity and decreased immunosuppressive cells.

Yang Y ，Che Y ，Zhao Y ，Wang X ... -  《-》

Increased Response of Human T-Lymphocytes by Dendritic Cells Pulsed with HPV16E7 and Pleurotus sajor-caju-β-glucan (PBG).

Roopngam PE 《-》

Mannose-Modified Liposome Co-Delivery of Human Papillomavirus Type 16 E7 Peptide and CpG Oligodeoxynucleotide Adjuvant Enhances Antitumor Activity Against Established Large TC-1 Grafted Tumors in Mice.

Previously, we demonstrated the therapeutic efficacy of a human papillomavirus (HPV) vaccine, including HPV16 E7 peptide and CpG oligodeoxynucleotides (CpG ODN), against small TC-1 grafted tumors. Here, we developed an HPV16 E7 peptide and CpG ODN vaccine delivered using liposomes modified with DC-targeting mannose, Lip E7/CpG, and determined its anti-tumor effects and influence on systemic immune responses and the tumor microenvironment (TME) in a mouse large TC-1 grafted tumor model. L-alpha-phosphatidyl choline (SPC), cholesterol (CHOL), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol-2000)] (DSPE-PEG-2000), 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and Mannose-PEG-DSPE, loaded with HPV16 E7 peptide and CpG ODN, were used to construct the Lip E7/CpG vaccine. The anti-tumor effects and potential mechanism of Lip E7/CpG were assessed by assays of tumor growth inhibition, immune cells, in vivo cytotoxic T lymphocyte (CTL) responses and cytokines, chemokines, CD31, Ki67 and p53 expression in the TME. In addition, toxicity of Lip E7/CpG to major organs was evaluated. Lip E7/CpG had a diameter of 122.21±8.37 nm and remained stable at 4°C for 7 days. Co-delivery of HPV16 E7 peptide and CpG ODN by liposomes exerted potent anti-tumor effects in large (tumor volume ≥200mm3) TC-1 grafted tumor-bearing mice with inhibition rates of 80% and 78% relative to the control and Free E7/CpG groups, respectively. Vaccination significantly increased numbers of CD4+ and CD8+ T cells, and IFN-γ-producing cells in spleens and tumors and enhanced HPV-specific CTL responses, while reducing numbers of inhibitory cells including myeloid-derived suppressor cells and macrophages. Expression of cytokines and chemokines was altered and formation of tumor blood vessels was reduced in the Lip E7/CpG group, indicating possible modulation of the immunosuppressive TME to promote anti-tumor responses. Lip E7/CpG did not cause morphological changes in major organs. Lip E7/CpG induced anti-tumor effects by enhancing cellular immunity and improving tumor-associated immunosuppression. Mannose-modified liposomes are the promising vaccine delivery strategy for cancer immunotherapy.

Zhao Y ，Wang H ，Yang Y ，Jia W ，Su T ，Che Y ，Feng Y ，Yuan X ，Wang X ... -  《International Journal of Nanomedicine》

Evaluation of immune responses induced by a novel human papillomavirus type 16 E7 peptide-based vaccine with Candida skin test reagent as an adjuvant in C57BL/6 mice.

Cell mediated immune (CMI) responses are crucial for the clearance of human papillomavirus (HPV) infection and HPV-associated lesions. Activated CD8 T cells are critical effector cells in recognizing and killing HPV-infected or HPV-transformed cells. CD4 T cells provide help for priming the generation and maintenance of CD8 T cells as well as for tumors immunity. An ideal therapeutic HPV peptide-based vaccine should induce both a robust CD8 T-cell response as well as a CD4 T-cell response for ensuring their efficiency. Candida skin test reagent was demonstrated to be able to induce the secretion of IL-12 by Langerhans cells and T-cell proliferation in vitro by our group, which indicated the potential of Candida to enhance CMI response. In this current study, we designed a novel HPV peptide-based vaccine which includes HPV16 E7 peptides and Candida as an adjuvant. The immune responses induced by the vaccine were comprehensively evaluated. The results showed that the vaccine induced significant HPV-specific CD8 T-cell and Th1 CD4 T-cell responses as well as humoral immune response. It is interesting that Candida alone induced a significant polarization of Th1 response an production of IFN-γ, which indicated Candida alone may be used as a potential immunotherapeutic reagent not only for HPV-associated lesions but also for other viral infection or even cancers.

Wang X ，Che Y ，Chen B ，Zhang Y ，Nakagawa M ，Wang X ... -  《-》

Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells.

Baghban Rahimi S ，Mohebbi A ，Vakilzadeh G ，Biglari P ，Razeghi Jahromi S ，Mohebi SR ，Shirian S ，Gorji A ，Ghaemi A ... -  《-》