Comparison on virulence and immunogenicity of two recombinant vaccinia vaccines, Tian Tan and Guang9 strains, expressing the HIV-1 envelope gene

PLoS One. 2012;7(11):e48343. doi: 10.1371/journal.pone.0048343. Epub 2012 Nov 6.

Abstract

Background: The vaccinia virus Guang9 strain (VG9), derived from the vaccinia virus Tian Tan strain (VTT) has been found to be less virulent than VTT.

Methodology/principal findings: To investigate whether VG9 could be a potential replicating virus vector, the TK genes in VG9 and VTT were replaced with the HIV-1 envelope gene via homologous recombination, resulting in the recombinant viruses, VG9-E and VTT-E. The biology, virulence, humoral and cellular immunological responses of VG9-E and VTT-E were evaluated. Our results indicated no obvious difference in range of host cells and diffusion between two recombinant viruses. Neurovirulence for VG9-E in weanling and suckling mice, and skin virulence in rabbits, were lower than that of VTT-E. The humoral immune responses, including binding antibody and neutralizing antibody responses, induced by VG9-E were not significantly different from those for VTT-E whilst IFN-γ response which represented cellular immune response induced by VG9-E was significantly higher than that did by VTT-E.

Conclusions/significance: Our results indicated that VG9-E was less virulent, yet induced higher cellular immune response than VTT-E. Therefore, it could be an ideal replicating vaccinia vector for HIV vaccine research and development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Cell Line
  • Enzyme-Linked Immunospot Assay
  • Female
  • HIV-1 / genetics*
  • Humans
  • Immunity / immunology
  • Interferon-gamma / immunology
  • Interleukin-2 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Rabbits
  • Skin / pathology
  • Skin / virology
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Vaccines, Synthetic / immunology*
  • Vaccinia virus / immunology*
  • Vaccinia virus / pathogenicity*
  • Viral Vaccines / immunology*
  • Virulence / immunology*
  • env Gene Products, Human Immunodeficiency Virus / genetics*
  • env Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Antibodies, Neutralizing
  • Interleukin-2
  • Vaccines, Synthetic
  • Viral Vaccines
  • env Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma

Grants and funding

This study was supported by grants from the National Science and Technology Major Project (2009ZX10004-801). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.