Induction of broadly neutralising HCV antibodies in mice by integration-deficient lentiviral vector-based pseudotyped particles

PLoS One. 2013 Apr 23;8(4):e62684. doi: 10.1371/journal.pone.0062684. Print 2013.

Abstract

Introduction: Integration-deficient lentiviral vectors (IDLVs) are a promising platform for immunisation to elicit both humoral immunity and cellular mediated immunity (CMI). Here, we compared the specific immunity in mice immunised via different regimens (homologous and cocktail) with IDLV-based HCV pseudoparticles (HCVpps) carrying pseudotyped glycoproteins E1E2 and bearing the HCV NS3 gene. Humoral and cell-mediated immune responses were also evaluated after IDLV-HCVpp immunisation combined with heterologous rAd5-CE1E2 priming protocols. Sera from the mice effectively elicited anti-E1, -E2, and -NS3 antibody responses, and neutralised various HCVpp subtypes (1a, 1b, 2a, 3a and 5a). No significant CMI was detected in the groups immunised with IDLV-based HCVpps. In contrast, the combination of rAd5-CE1E2 priming and IDLV-based HCVpp boosting induced significant CMI against multiple antigens (E1, E2, and NS3).

Conclusion: IDLV-based HCVpps are a promising vaccination platform and the combination of rAd5-CE1E2 and IDLV-based HCVpp prime-boost strategy should be further explored for the development of a cross-protective HCV vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Cell Line
  • Cross Protection / immunology
  • Female
  • Gene Order
  • Genetic Vectors / genetics*
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C Antibodies / blood
  • Hepatitis C Antibodies / immunology*
  • Humans
  • Immunity, Humoral
  • Immunization
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lentivirus / genetics*
  • Mice
  • Virion / immunology*
  • Virion / ultrastructure
  • Virus Integration

Substances

  • Antibodies, Neutralizing
  • Hepatitis C Antibodies
  • Immunoglobulin G

Grants and funding

This study was supported by the 863 Hi-Tech Research and Development Program of China (2007AA02Z455) and the National Mega-project for Infectious Diseases of China (2009ZX10004-705 and -715). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.