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At least 109 records · Page 6Linked to original sources
PubMed2000

Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model.

Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths per year. A vaccine against TB more potent than the current live vaccine, bacillus Calmette-Guérin (BCG), is desperately needed. Using two commercially available strains of BCG as host strains, BCG Connaught and Tice, we have constructed two recombinant BCG vaccines stably expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the primary causative agent of TB. 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 BCG vaccines. The recombinant vaccines are the first vaccines against TB more potent than the current commercially available BCG vaccines, which were developed nearly a century ago.

Animals↗
PubMed2003

Increased neutrophil influx but no impairment of protective immunity to tuberculosis in mice lacking the CD44 molecule.

Up-regulation of expression of the cell-surface marker CD44 is a major characteristic of T lymphocytes responding in the lungs of mice infected with Mycobacterium tuberculosis. These lymphocytes express an activated/memory phenotype as seen by their high expression of the CD44 molecule and low expression of CD62L and CD45RB cell-surface molecules. Based on increasing evidence that the CD44 molecule participates in several aspects of the inflammatory response, we evaluated its role in the response to infection with M. tuberculosis using gene-disrupted mice. In this report, we show that CD44 expression is not necessary for the proper trafficking of protective cells to the lungs of mice infected with M. tuberculosis or the direct expression of protective immunity leading to control and containment of the bacterial load in this organ. However, although there were no differences in the bacterial load or migration of activated T lymphocytes to the inflamed lung, the absence of the CD44 molecule resulted in a substantially increased accumulation of neutrophils in the lung. These data indicate that loss of CD44 expression does not alter expression of T helper cell type 1 immunity to tuberculosis in the lungs but has major effects on the overall cellular composition of the immunopathological response.

Animals↗
PubMed1991

Rapid serodiagnostic test for pulmonary tuberculosis.

Immune complexes (ICs) were isolated from sera of patients with pulmonary tuberculosis (PT), non-tuberculous pulmonary diseases and healthy control subjects by polyethylene glycol (PEG) precipitation method. Specific mycobacterial antibody in ICs was tested against an affinity purified mycobacterial antigen by counter-current immunoelectrophoresis (CIE). The results show that specific mycobacterial antibodies are present only in ICs of patients with PT (70%). Therefore CIE could be used as a simple and rapid serodiagnostic test in patients with PT, particularly when bacteriological methods in sputum specimens are negative for Mycobacterium tuberculosis. CIE has several operational advantages over ELISA and best suited to laboratories with limited resources.

Counterimmunoelectrophoresis↗
PubMed1976

Effect of rifampin on immunity to tuberculosis and on delayed hypersensitivity to purified protein derivative.

Mice vaccinated with mycobacterial ribonucleic acid (RNA) produced a high immune response and did not develop delayed hypersensitivity to purified protein derivative (PPD), and rifampin had no effect on the immune response. Mice vaccinated with viable H37Ra cells produced a high immune response and did develop delayed hypersensitivity to PPD. Rifampin had no effect on this immune response, but reduced the footpad reactions to PPD. Both mycobacterial RNA and poly(A:U) served as adjuvants for induction of hypersensitivity to PPD. This hypersensitivity was reduced by the administration of rifampin. Rifampin had no effect on the production of mycobacterial growth inhibitory factor, which is produced following vaccination of mice with mycobacterial RNA or viable H37Ra cells. Rifampin had no effect on the nonspecific phase of the granulomatous response, but did inhibit the secondary allergic phase of this response. The action, therefore, of rifampin that inhibits the induction of delayed hypersensitivity but had no effect on the immune responses against tuberculosis leads to a separation of tuberculin hypersensitivity from cellular immunity to tuberculosis.

Animals↗