期刊
JOURNAL OF INFECTIOUS DISEASES
卷 207, 期 5, 页码 778-785出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis751
关键词
tuberculosis; vaccine; sulfate metabolism; human immune response; ATP sulfurylase
资金
- National Health and Medical Research Council of Australia [570768]
- University of Sydney
- National Institutes of Health [GM54469]
- New South Wales Department of Health
New therapies to control tuberculosis are urgently required because of the inability of the only available vaccine, BCG, to adequately protect against tuberculosis. Here we demonstrate that proteins of the Mycobacterium tuberculosis sulfate-assimilation pathway (SAP) represent major immunogenic targets of the bacillus, as defined by strong T-cell recognition by both mice and humans infected with M. tuberculosis. SAP proteins displayed increased expression when M. tuberculosis was resident within host cells, which may account in part for their ability to stimulate anti-M. tuberculosis host immunity. Vaccination with the first enzyme in this pathway, adenosine-5'-triphosphate sulfurylase, conferred significant protection against murine tuberculosis and boosted BCG-induced protective immunity in the lung. Therefore, we have identified SAP components as a new family of M. tuberculosis antigens, and we have demonstrated that these components are promising candidate for inclusion in new vaccines to control tuberculosis in humans.
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