title: MPG-based nanoparticle: An efficient delivery system for enhancing the potency of DNA vaccine expressing HPV16E7.
abstract: DNA vaccines against human papillomavirus (HPV) type 16 have not been successful in clinical trials, due to the lack of an appropriate delivery system. In this study, a peptide-based gene delivery system, MPG, which forms stable non-covalent nanoparticles with nucleic acids, was used for in vitro and in vivo delivery of HPV16 E7 DNA as a model antigen. The results demonstrated that at Nitrogen/Phosphate (N/P) ratio over 10:1, this peptide can effectively condense plasmid DNA into stable nanoparticles with an average size of 180-210nm and a positive surface charge. The transfection efficiency of MPG-based nanoparticles was shown to be comparable with Polyethyleneimine (PEI). The efficient protein expression detected by western blotting and flow cytometry supports the potential of MPG-based nanoparticles as a potent delivery system in DNA vaccine formulations. Immunization with MPG/E7DNA nanoparticles at an N/P ratio of 10:1 induced a stronger Th1 cellular immune response with a predominant interferon-γ (IFN-γ) profile than those induced by E7DNA alone in a murine tumor model. These findings suggest that MPG peptide as a novel gene delivery system could have promising applications in improving HPV therapeutic vaccines.
authors.affiliation: Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Saleh
authors.affiliation: Department of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, Iran. Electronic address: A_bolhasani@pasteur.ac.ir.
authors.forename: Azam
authors.initials: A
authors.lastname: Bolhassani
authors.affiliation: Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran. Electronic address: shoja_sa@modares.ac.ir.
authors.forename: Seyed Abbas
authors.initials: SA
authors.lastname: Shojaosadati
authors.affiliation: Department of Hepatitis and AIDs, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Aghasadeghi
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D004268:DNA-Binding Proteins; D018014:Gene Transfer Techniques; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009584:Nitrogen / Q000737:chemistry; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D010710:Phosphates / Q000737:chemistry; D014162:Transfection; D064166:Vaccine Potency; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*
chemical_list: D057846:Cell-Penetrating Peptides; D004268:DNA-Binding Proteins; C475074:MPG peptide; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D010710:Phosphates; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma; D009584:Nitrogen
keywords: Cell-penetrating peptide; DNA vaccine; E7; Gene delivery system; Human papillomavirus