title: An ESAT-6:CFP10 DNA vaccine administered in conjunction with Mycobacterium bovis BCG confers protection to cattle challenged with virulent M. bovis.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Maue
authors.forename: W Ray
authors.initials: WR
authors.lastname: Waters
authors.forename: Mitchell V
authors.initials: MV
authors.lastname: Palmer
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nonnecke
authors.forename: F Chris
authors.initials: FC
authors.lastname: Minion
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Brown
authors.forename: Junzo
authors.initials: J
authors.lastname: Norimine
authors.forename: Monica R
authors.initials: MR
authors.lastname: Foote
authors.forename: Charles F C
authors.initials: CF
authors.lastname: Scherer
authors.forename: D Mark
authors.initials: DM
authors.lastname: Estes
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018122:B7-1 Antigen / Q000008:administration & dosage / Q000276:immunology; D051940:B7-2 Antigen / Q000008:administration & dosage / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D002417:Cattle; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001500:BCG Vaccine; C505464:ESAT-6-CFP10 fusion protein; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor