Tuberculosis remains a serious and common disease worldwide. In the U.S. emergence of multi-antibiotic resistant strains, due to the rapid passage of Mycobacterium tuberculosis in patients with AIDS, poses a public health problem. Although the most frequently used vaccine in the world, there is no scientifically-based evidence that BCG prevents primary pulmonary tuberculosis and its protective effect against meningitis in children has not been related with a protective antigen or a host immune component. Our research into a new vaccine for tuberculosis is based upon the similarity of primary infection caused by M. tuberculosis with that of capsulated bacterial respiratory pathogens, viz: 1) epidemiologic data which show that tuberculous meningitis has a similar age distribution as capsulated bacteria; 2) the presence of a capsular polysaccharide on M. tuberculosis and other mycobacteria in vitro and in vivo; and 3) BCG and protein components of this and wild-type strains induce prolonged survival but do not protect animals against challenge with wild-type M. tuberculosis. We identified alpha(1 >2) glucose moiety in extracts of M. tuberculosis, but not in BCG, by its reactivity with pneumococcal type 12F typing antisera were not- productive. Almost all the polysaccharide extracted with saline from Mycobacteria was a glycogen-like molecule composed exclusively of D-glucose. Only a trace of this material precipitates with pneumococcal type 12F antisera and gives an identity reaction with dextran 1299 which has kojibiose residues. Conjugates prepared with kojipentaose did not elicit opsonophagocytic killing and did not protect mice against challenge with M. tuberculosis. Conjugates prepared with a conjugate of the glycogen-like molecule in two strains of M. tuberculosis induced opsonphagocytic killing and protected mice against challenge with wild-type M. tuberculosis.
| 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 |
