An ESAT-6:CFP10 DNA vaccine administered in conjunction with Mycobacterium bovis BCG confers protection to cattle challenged with virulent M. bovis

Vaccine. 2007 Jun 11;25(24):4735-46. doi: 10.1016/j.vaccine.2007.03.052. Epub 2007 Apr 24.


The potency of genetic immunization observed in the mouse has demonstrated the utility of DNA vaccines to induce cell-mediated and humoral immune responses. However, it has been relatively difficult to generate comparable responses in non-rodent species. The use of molecular adjuvants may increase the magnitude of these suboptimal responses. In this study, we demonstrate that the co-administration of plasmid-encoded GM-CSF and CD80/CD86 with a novel ESAT-6:CFP10 DNA vaccine against bovine tuberculosis enhances antigen-specific cell-mediated immune responses. ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA vaccinated animals exhibited significant (p<0.01) antigen-specific proliferative responses compared to other DNA vaccinates. Increased expression (p< or =0.05) of CD25 on PBMC from ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA vaccinates was associated with increased proliferation, as compared to control DNA vaccinates. Significant (p<0.05) numbers of ESAT-6:CFP10-specific IFN-gamma producing cells were evident from all ESAT-6:CFP10 DNA vaccinated animals compared to control DNA vaccinates. However, the greatest increase in IFN-gamma producing cells was from animals vaccinated with ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA. In a low-dose aerosol challenge trial, calves vaccinated as neonates with Mycobacterium bovis BCG and ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA exhibited decreased lesion severity in the lung and lung-associated lymph nodes following viruluent M. bovis challenge compared to other vaccinated animals or non-vaccinated controls. These data suggest that a combined vaccine regimen of M. bovis BCG and a candidate ESAT-6:CFP10 DNA vaccine may offer greater protection against tuberculosis in cattle than vaccination with BCG alone.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • B7-1 Antigen / administration & dosage
  • B7-1 Antigen / immunology
  • B7-2 Antigen / administration & dosage
  • B7-2 Antigen / immunology
  • BCG Vaccine / immunology*
  • Cattle
  • Cell Proliferation
  • Disease Models, Animal
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Interferon-gamma / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Lung / pathology
  • Lymph Nodes / pathology
  • Lymphocytes / chemistry
  • Lymphocytes / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Tuberculosis, Bovine / immunology*
  • Tuberculosis, Bovine / pathology
  • Tuberculosis, Bovine / prevention & control
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*


  • Adjuvants, Immunologic
  • B7-1 Antigen
  • B7-2 Antigen
  • BCG Vaccine
  • ESAT-6-CFP10 fusion protein
  • Interleukin-2 Receptor alpha Subunit
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor