Enhanced protective efficacy and reduced viral load of foot-and-mouth disease DNA vaccine with co-stimulatory molecules as the molecular adjuvants

Antiviral Res. 2007 Oct;76(1):11-20. doi: 10.1016/j.antiviral.2007.04.002. Epub 2007 May 21.

Abstract

To improve efficacy of DNA vaccination, various approaches have been developed, including the use of plasmid expressing co-stimulatory molecules as molecular adjuvants. In this study, we investigated whether co-inoculation of a construct expressing either 4-1BBL or OX40L as the molecular adjuvant with FMDV DNA vaccine, pcD-VP1, can increase immune responses and protective efficacies. Compared to the group immunized with pcD-VP1 alone, the co-inoculation of either molecular adjuvant induced a higher ratio of IgG2a/IgG1, higher levels of expression of IFN-gamma in CD4(+) and CD8(+) T cells and antigen-specific CTL responses, and more importantly provided an enhanced protection against the live FMDV challenge in animals. Concurrently, 4-1BBL as the molecular adjuvant dramatically reduced the viral loads of FMDV in vivo after the challenge. Together, the results demonstrate that co-stimulatory molecules 4-1BBL and OX40L can enhance the antigen-specific cell-mediated responses elicited by VP1 DNA vaccine and provide an enhanced protective efficacy with the reduced viral loads.

MeSH terms

  • 4-1BB Ligand / administration & dosage*
  • 4-1BB Ligand / biosynthesis
  • 4-1BB Ligand / genetics
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / biosynthesis
  • Adjuvants, Immunologic / genetics
  • Animals
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cytotoxicity Tests, Immunologic
  • Female
  • Foot-and-Mouth Disease / blood
  • Foot-and-Mouth Disease / immunology*
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease / virology
  • Foot-and-Mouth Disease Virus / immunology*
  • Guinea Pigs
  • HeLa Cells
  • Humans
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • OX40 Ligand / administration & dosage*
  • OX40 Ligand / biosynthesis
  • OX40 Ligand / genetics
  • Vaccination*
  • Vaccines, DNA / administration & dosage
  • Viral Load
  • Viral Vaccines / administration & dosage*

Substances

  • 4-1BB Ligand
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin G
  • OX40 Ligand
  • Vaccines, DNA
  • Viral Vaccines
  • Interferon-gamma