Protein vaccination with HPV16 E7/Pep-1 nanoparticles elicits a protective T-helper cell-mediated immune response

IUBMB Life. 2016 Jun;68(6):459-67. doi: 10.1002/iub.1503. Epub 2016 Apr 19.

Abstract

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.

Keywords: E7; Pep-1; cell penetrating peptide; cervical cancer; human papillomavirus; therapeutic vaccine.

MeSH terms

  • Animals
  • Cysteamine / administration & dosage
  • Cysteamine / analogs & derivatives*
  • Cysteamine / chemistry
  • Cytokines / metabolism
  • Drug Delivery Systems / methods
  • Female
  • HEK293 Cells
  • Humans
  • Immunity, Cellular / drug effects
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / prevention & control
  • Neoplasms, Experimental / virology
  • Papillomavirus E7 Proteins / administration & dosage*
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / immunology
  • Papillomavirus Vaccines / pharmacology
  • Particle Size
  • Peptides / administration & dosage
  • Peptides / chemistry*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*

Substances

  • Cytokines
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Pep-1 peptide
  • Peptides
  • oncogene protein E7, Human papillomavirus type 16
  • Cysteamine