[Frontiers in Bioscience 3, c27-33, May 1, 1998] |
LURIE’S TUBERCLE-COUNT METHOD TO TEST TB VACCINE EFFICACY IN RABBITS
Departments of Environmental Health Sciences, Molecular Microbiology and Immunology, and Epidemiology, School of Hygiene and Public Health; and the Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205
Received 3/9/98 Accepted 3/14/98
7. EFFECTS OF VACCINES ON THE 5 STAGES OF TUBERCULOSIS (13,14,17,18)
7.1 Stage 1. Destruction of the bacillus by alveolar macrophages
Vaccines have no effect on the power of alveolar macrophages to destroy tubercle bacilli, after the nonspecific adjuvant effects of the vaccine have subsided.
7.2 Stage 2. Symbiosis
Vaccines markedly shorten the stage of symbiosis, in which the bacillus is growing logarithmically in the non-activated macrophages infiltrating from the bloodstream, because acquired immunity occurs more rapidly in immunized host.
7.3 Stage 3. Initial caseous necrosis
Vaccines enable bacilli-laden macrophages to be killed sooner, causing caseous necrosis to occur sooner and stopping the logarithmic growth of the bacillus sooner. The bacillus cannot multiply in solid caseous material.
7.4 Stage 4. Progression or regression of the established primary tubercle
Vaccines hasten the activation of blood-derived infiltrating macrophages. The now-activated macrophages ingest and inhibit bacilli escaping from the solid caseous center, thereby preventing renewed intracellular bacillary growth. In other words, vaccines decrease the progression of established tubercles and hasten their regression.
7.5 Stage 5. Liquefaction and cavity formation
Vaccines, given before the onset of the disease, may or may not hasten liquefaction and cavity formation. Vaccines may or may not affect the extracellular growth of tubercle bacilli in liquefied caseum and cavities. Also, such vaccines may or may not enhance host immunity at this stage of tuberculosis, because by this time the disease itself has caused the host to develop considerable immunity. Since susceptibility to the tuberculin-like products of the bacillus is apparently a major cause of liquefaction and cavity formation (19-21), vaccines that produce little sensitivity to tuberculin should be favored over those that produce more, if they are equally effective in preventing clinical disease (see 22).
The tubercle-count method measures the vaccine’s ability to prevent microscopic tubercles from reaching grossly visible size by affecting Stages 2, 3 and 4. In other words, it measures the vaccine's ability to shorten the symbiotic stage, hasten the onset of caseation, and activate blood-derived macrophages more rapidly.