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Title:   Author  item
                                            Waters, Wadeitem
                                            Palmer, Mitchellitem
                                            Nonnecke, Brianitem
                                            Thacker, Tyleritem
                                            SCHERER, CHARLES - UNIV. OF TX MED. BR.item
                                            ESTES, D - UNIV. OF TX MED. BR.item
                                            JACOBS, WILLIAM - HOWARD HUGHES MEDICAL Iitem
                                            GLATMAN-FREEDMAN, AHARONA - ALBERT EINSTEIN COLL.item
                                            LARSEN, MICHELLE - HOWARD HUGHES MED. INSTI.
  Submitted to: Vaccine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 9/16/2007
                                    Publication  Date: 11/7/2007
                                    Citation: Waters, W.R., Palmer, M.V., Nonnecke, B.J., Thacker, T.C., Scherer, C.F., Estes, D.M., Jacobs, W.R., Glatman-Freedman, A., Larsen, M.H. 2007. Failure of a Mycobacterium tuberculosis DeltaRD1 DeltapanCD Double Deletion Mutant in a Neonatal Calf Aerosol M. bovis Challenge model: Comparisons to Responses Elicited by M. bovis bacille Calmette Guerin. Vaccine. 25(45):7832-7840.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 techniques are needed for prevention of tuberculosis in cattle. In this study, a bovine model for evaluation of improved vaccines is described. Knowledge obtained from this study will assist in the development of new vaccines for prevention of tuberculosis in cattle.
                                Technical Abstract: An attenuated Mycobacterium tuberculosis RD1 knockout x pantothenate auxotroph (mc**2 6030) vaccine failed to protect neonatal calves from a low dose, aerosol M. bovis challenge. In contrast, M. bovis bacille Calmette Guerin (BCG)-vaccinates had reduced tuberculosis-associated pathology as compared to non- and mc**2 6030-vaccinates. Mycobacterial colonization was not impacted by vaccination. Positive prognostic indicators associated with reduced pathology in the BCG-vaccinated group included: decreased antigen induced IFN-gamma, iNOS, IL-4, and MIP1-alpha responses and a diminished activation phenotype (i.e., decreased CD25+ and CD44+ cells and increased CD62L+ cells) in mycobacterial-stimulated mononuclear cell cultures. The calf sensitization and challenge model provides an informative screen for candidate tuberculosis vaccines before their evaluation in costly non-human, primates.


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