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
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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DOI：
10.1016/j.vaccine.2007.08.029
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发表时间：
2007-11-07
期刊：
影响因子：
5.5
通讯作者：
Larsen, Michelle H.
中科院分区：
文献类型：
--
作者：
Waters, W. Ray;Palmer, Mitchell V.;Larsen, Michelle H.
在2周龄时接种的减毒结核分枝杆菌RD1敲除和泛酸营养不良（mc(2)6030）疫苗未能保护犊牛免受2.5月龄时低剂量气溶胶牛分枝杆菌的攻击。相比之下，与未接种和接种mc2 6030疫苗相比，接种牛乳杆菌卡介苗（BCG）疫苗减少了结核病相关病理。分枝杆菌定植不受疫苗接种的影响。与bcg免疫组病理减少相关的阳性预后指标是抗原诱导的ifn - γ、iNOS、IL-4和MIP 1- α反应减少，抗原诱导的FoxP3表达增加，以及在分枝杆菌刺激的单核细胞培养中活化表型减少（即CD25+和CD44+细胞向下箭头和CD62L+细胞向上箭头）。小牛致敏和激发模型为候选结核病疫苗在昂贵的非人类灵长类动物中进行评估之前提供了信息丰富的筛选。Elsevier Ltd.出版。
An attenuated Mycobacterium tuberculosis RD1 knockout and pantothenate auxotroph (mc(2)6030) 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 mc(2)6030-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-gamma, iNOS, IL-4, and MIP 1-alpha responses, increased antigen induced FoxP3 expression, and a diminished activation phenotype (i.e., down arrow CD25+ and CD44+ cells and up arrow 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. Published by Elsevier Ltd.