Worldwide, tuberculosis remains a serious cause of morbidity and mortality: in the U.S., emergence of multi-antibiotic-resistant strains is probably due to the rapid passage of the pathogen in patients with AIDS. Although it is the most frequently used vaccine in the world, there is no good evidence that BCG prevents primary pulmonary tuberculosis. The development of a new vaccine for M. tuberculosis is based upon its similarity with capsulated bacteria: 1) serum antibody-mediated opsonphagocytosis by peripheral blood polymorphonuclear leukocytes; 2) the presence of a capsular polysaccharide (denoted as electron translucent zone); 3) similar age incidence of tuberculous as well as cpasulated bacterial meningitis; and 4) in-vivo evidence for protective immunity related to serum antibodies to Polysaccharide II of Seibert (poly alpha (1 to 2) glucose. M. tuberculosis strains H37Rv, DL and Erdmann have been cultivated in synthetic media. Organisms inactivated with 70% ethanol and surface structures removed by extraction in saline and then in Triton X-100. Both preparations showed glycogen and a cell wall saccharide, lipoarabinomannan. The cell pellet of strain Erdmann only released a saccharide reactive with pneumococcus type 12F antiserum similar to the reaction of this antiserum with dextran 1299 shown to have kojibiose, a di alpha(12) glucose. Several freshly isolated strains, from the blood and pleural fluid are being investigated for their content of the Polysaccharide II-like structure. Murine monoclonal antibodies, induced by immunization with inactivated M. tuberculosis with specificity for alpha(1 to 2) glucose linkages are under investigation for their in-vitro opsonphagocytic effect.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Schwebach, J R; Casadevall, A; Schneerson, R et al. (2001) Expression of a Mycobacterium tuberculosis arabinomannan antigen in vitro and in vivo. Infect Immun 69:5671-8