An ESAT-6:CFP10 DNA vaccine administered in conjunction withMycobacterium bovisBCG confers protection to cattle challenged with virulentM. bovis

• Published in: Vaccine Vol. 25; no. 24; p. 4735
• Main Authors: Maue, Alexander C, Waters, W Ray, Palmer, Mitchell V, Nonnecke, Brian J, Minion, F Chris, Brown, Wendy C, Norimine, Junzo, Foote, Monica R, Scherer, Charles FC, Estes, D Mark
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 11.06.2007
• Subjects: Animals; Cattle; Deoxyribonucleic acid; DNA; Immune system; Immunization; Lymph nodes; Neonates; Plasmids; Tuberculosis; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.03.052

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<=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-γ producing cells were evident from all ESAT-6:CFP10 DNA vaccinated animals compared to control DNA vaccinates. However, the greatest increase in IFN-γ 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 withMycobacterium bovisBCG and ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA exhibited decreased lesion severity in the lung and lung-associated lymph nodes following viruluentM. bovischallenge compared to other vaccinated animals or non-vaccinated controls. These data suggest that a combined vaccine regimen ofM. bovisBCG and a candidate ESAT-6:CFP10 DNA vaccine may offer greater protection against tuberculosis in cattle than vaccination with BCG alone.