Failure of a Mycobacterium tuberculosis ΔRD1 ΔpanCD double deletion mutant in a neonatal calf aerosol M. bovis challenge model: Comparisons to responses elicited by M. bovis bacille Calmette Guerin
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- 作者：W. Ray Waters ; Mitchell V. Palmer ; Brian J. Nonnecke ; Tyler C. Thacker ; Charles F. Capinos Scherer ; D. Mark Estes ; William R. Jacobs Jr. ; Aharona Glatman-Freedman ; Michelle H. Larsen
- 关键词：Tuberculosis ; Live bacterial vaccine ; Auxotroph ; BCG ; Neonatal calf ; Aerosol Inoculation ; FoxP3
- 刊名：Vaccine
- 出版年：2007
- 出版时间：7 November 2007
- 年：2007
- 卷：25
- 期：45
- 页码：7832-7840
- 全文大小：661 K
文摘
An attenuated Mycobacterium tuberculosis RD1 knockout and pantothenate auxotroph (mc26030) vaccine administered at 2 weeks of age failed to protect calves from low dose, aerosol M. bovis challenge at 2.5 months of age. In contrast, M. bovis bacille Calmette Guerin (BCG)-vaccinates had reduced tuberculosis-associated pathology as compared to non- and mc26030-vaccinates. Mycobacterial colonization was not impacted by vaccination. Positive prognostic indicators associated with reduced pathology in the BCG-vaccinated group were decreased antigen induced IFN-γ, iNOS, IL-4, and MIP1-α responses, increased antigen induced FoxP3 expression, and a diminished activation phenotype (i.e., ↓CD25+ and CD44+ cells and ↑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.