期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 97, 期 25, 页码 13853-13858出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.250480397
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资金
- NIAID NIH HHS [AI31338, R01 AI031338] Funding Source: Medline
Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against Tn more potent than the current live vaccine, bacillus Calmette-Guerin (BCG). is desperately needed. Using two commercially available strains of BCC as host strains, BCC Connaught and Tice, we have constructed two recombinant BCC vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of Tn. We have tested the efficacy of the two strains in the highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB. Animals immunized with the recombinant BCG vaccines and challenged by aerosol with a highly Virulent strain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG Vaccine counterparts. Statistically, these differences were highly significant. Paralleling these results, at necropsy, animals immunized with the recombinant BCG vaccines had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCC vaccines. The recombinant Vaccines are the first Vaccines against TB more potent than the current commercially available BCC vaccines, which were developed nearly a century ago.
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