Protein vaccination with HPV16 E7/Pep-1 nanoparticles elicits a protective T-helper cell-mediated immune response.
Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPV-associated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h post-transfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-γ levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines. © 2016 IUBMB Life, 68(6):459-467, 2016.
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.|Department of Biotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
Golnaz
G
Mardani
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Azam
A
Bolhassani
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Elnaz
E
Agi
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Sepideh
S
Shahbazi
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Seyed
S
Mehdi Sadat
D000818:Animals; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000517:prevention & control / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage* / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C503924:Pep-1 peptide; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16; D003543:Cysteamine
E7; Pep-1; cell penetrating peptide; cervical cancer; human papillomavirus; therapeutic vaccine