Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/30/2007
Publication Date: 4/24/2007
Citation: Maue, A.C., Waters, W.R., Palmer, M.V., Nonnecke, B.J., Minion, F.C., Brown, W.C., Norimine, J., Foote, M., Scherer, C.F., Estes, D.M. 2007. An ESAT-6:CFP10 DNA vaccine Administered in Conjunction with Mycobacterium bovis BCG confers Protection to Cattle Challenged with Virulent M. bovis. Vaccine. 25(24):4735-4746. Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States. Improved strategies to prevent tuberculosis infection in cattle and wildlife species are needed. In the present study, a novel experimental tuberculosis vaccine was evaluated for activity in the induction of an immune response. The immune response was enhanced when a host stimulatory factor was included with the vaccine. These findings indicate that new and improved vaccines may prove superior to traditional TB vaccines.
Technical 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 < 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 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.