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Title:   Author  item
                                            MAUE, ALEXANDER - UNIV. OF MISSOURIitem
                                            Waters, Wadeitem
                                            Palmer, Mitchellitem
                                            Nonnecke, Brianitem
                                            MINION, F - IOWA STATE UNIV.item
                                            BROWN, WENDY - WASHINGTON ST. UNIV.item
                                            NORIMINE, JUNZO - WASHINGTON ST. UNIV.item
                                            FOOTE, MONICA - IOWA STATE UNIV.item
                                            SCHERER, CHARLES - UNIV. OF TX MED. BRANCHitem
                                            ESTES, D - UNIV. OF TX MED. BRANCH
  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.


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