Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis.

Abstract

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are can-

Extraordinarily few organisms of a live recombinant BCG vaccine against tuberculosis induce maximal cell-mediated and protective immunity

“…Few animals immunized with the low dose (10 1 CFU) developed antibody titers above background and even then the titers were modest. In contrast, animals immunized with the high dose (1,2,(23)(24)(25)(26). In this regard, the 30 kDa protein is the major protein secreted by M. tuberculosis in broth culture (24) and among the most abundantly expressed proteins of all types produced by M. tuberculosis within human macrophages (27).…”

“…In contrast, animals immunized with the high dose (1,2,(23)(24)(25)(26). In this regard, the 30 kDa protein is the major protein secreted by M. tuberculosis in broth culture (24) and among the most abundantly expressed proteins of all types produced by M. tuberculosis within human macrophages (27). Second, the 30 kDa protein has a large number of immunodominant T-cell epitopes in both guinea pigs and humans (28,29), allowing it to induce immunoprotection across disparate MHC types in outbred populations.…”

A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG

“…r30 was purified as described from culture filtrates of recombinant Mycobacterium smegmatis 1-2c containing plasmid pMTB30 and demonstrated to be indistinguishable from the native protein [15,16]. The extent (diameter) of induration was assessed 24 hr later by palpation and inspection in direct and oblique light.…”

β-Lactamase can function as a reporter of bacterial protein export during Mycobacterium tuberculosis infection of host cells

“…In fact, no colonies of the strain expressing the truncated 9BlaTEM-1 grew on agar containing carbenicillin even after extended incubation (Figs 1 and 2). However, expression of a hybrid protein composed of a Sec signal sequence from Mpt63, a well-established secreted protein of M. tuberculosis (Horwitz et al, 1995;Manca et al, 1997), fused to 9BlaTEM-1 (ssMpt63-9BlaTEM-1) protected the DblaC mutant from carbenicillin, as was evident by the ability of this strain to grow on carbenicillin agar plates (Figs 1 and 2) . We similarly tested a fusion protein in which the Sec signal sequence of a proven cellwall-associated lipoprotein, Mpt83 (Hewinson et al, 1996), was fused to 9BlaTEM-1.…”