title: A novel self-assembled nanoparticle vaccine with HIV-1 Tat₄₉₋₅₇/HPV16 E7₄₉₋₅₇ fusion peptide and GM-CSF DNA elicits potent and prolonged CD8⁺ T cell-dependent anti-tumor immunity in mice.
abstract: Peptide-based vaccines derived from the E7 protein of human papillomavirus (HPV) type 16 were developed to induce effective T cell responses against established cervical cancer, but have met with limited clinical success. It is necessary to develop novel peptide-based strategies to substantially improve the immune response against HPV16-related cancer. In this study, we aimed to design a novel peptide-based self-assembled nanoparticle HPV16 vaccine by combining the cell-penetrating peptide HIV-1 Tat(49-57) that was fused with the HPV16 E7(49-57) cytotoxic T lymphocyte (CTL) epitope and the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, and to investigate how it improves the immune response and the therapeutic outcome ex vivo and in vivo. Nanoparticles were prepared and identified by transmission electron microscopy (TEM), gel retardation and DNase I protection assays. This type of vaccine formulation formed the 20-80 nm nanoparticles, and greatly improved epitope-specific immunity both ex vivo and in vivo. Importantly, this vaccine type was associated with decreased tumor growth and enhanced long-term survival in the prophylactic and therapeutic mouse models. The underlying mechanisms were determined to involve priming of enhanced frequency of CD8(+) memory T subtype cells. These results suggest that the nanoparticle Tat-E7/pGM-CSF represents a promising novel approach to enhance the potency of peptide-based cervical cancer vaccines, and this vaccine design strategy may act as a useful reference for research of virus-associated diseases and specific tumor immunotherapies.
authors.affiliation: Department of Dermatology, Southwestern Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Rui
authors.initials: R
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.forename: Zeming
authors.initials: Z
authors.lastname: Huang
authors.forename: Jinglei
authors.initials: J
authors.lastname: Shi
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D016178:Granulocyte-Macrophage Colony-Stimulating Factor