Characterization and evaluation of the immune responses elicited by a novel human papillomavirus (HPV) therapeutic vaccine: HPV 16E7-HBcAg-Hsp65 fusion protein

J Virol Methods. 2014 Mar:197:1-6. doi: 10.1016/j.jviromet.2013.10.033. Epub 2013 Nov 28.

Abstract

Human papillomaviruses (HPV), particularly HPV16, are associated with most cervical cancers. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines. In this study, a novel fusion protein, HPV 16 E7-HBcAg-Hsp65 (VR111), with the goal of increasing anti-HPV16 cellular immunity was developed. VR111 was analyzed using SDS-PAGE, western-blotting, capillary isoelectric focusing (cIEF), analytical ultracentrifugation (AUC) and dynamic light scattering (DLS). Gamma interferon (IFN-γ) secretion assay was performed by enzyme-linked immunospot (ELISPOT) and ELISA to test their ability to induce cellular immune response. Significant correlation between ELISPOT and ELISA was observed (r=0.8680, p<0.0001). It was shown that VR111 could induce a significant increase in E7-specific CD8(+) T cell responses. Humoral immune response was also observed. The antibody titer levels were measured by ELISA. These results indicated that VR111 was a promising therapeutic vaccine for treatment of cervical cancer with possible therapeutic potential in clinical settings.

Keywords: Cellular immune response; Human papillomaviruses; Humoral immune response; Immunogenicity; Therapeutic vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunospot Assay
  • Female
  • Heat-Shock Proteins / genetics
  • Hepatitis B Core Antigens / genetics
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Infections / therapy*
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Viral
  • Heat-Shock Proteins
  • Hepatitis B Core Antigens
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • heat-shock protein 65, human
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma