Host-Parasite Relationships in Experimental Airborne Tuberculosis I. Preliminary Studies in BCG-Vaccinated and Nonvaccinated Animals

Abstract

Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and nonvaccinated animals. J. Bacteriol. 91:718-724. 1966.-Previous studies from this laboratory on immunogenicity and allergenicity of defatted mycobacterial vaccines involved subcutaneous challenge of guinea pigs and killing of the animals 6 weeks later to evaluate the amount of disease. This type of experiment has been discontinued in this laboratory in favor of an airborne challenge type of experiment, with the advantages that aniimals can be challenged with small numbers of bacilli by a natural route, and the number of primary lesions, the rate of spread from those lesions, and the rate of bacillary multiplication can be used to evaluate protection. Experiments to determine uniformity of infection showed that a fair degree of uniformity resulted when seven guinea pigs were exposed simultaneously, and were studied 3 weeks later to determine numbers of primary lesions and bacilli in the tissues. A less satisfactory degree of uniformity was obtained when more animals were exposed at one time. BCG-vaccinated and nonvaccinated animals were studied to determine the earliest time and the optimal time for killing the animals to detect the effects of vaccination. In guinea pigs, the degree of protection assessed by lesion counts is time-dependent, but the degree of protection assessed by viable counts of bacilli in the tissues was relatively constant 3 to 12 weeks after infection. Mice vaccinated subcutaneously with BCG were not protected against infection at any interval between 2 and 19 weeks. Guinea pigs vaccinated subcutaneously with the same lot of vaccine were protected as judged by counts of viable bacilli in the tissues 3 weeks after infection.

Properties and protective value of the secondary versus primary T helper type 1 response to airborne Mycobacterium tuberculosis infection in mice

“…It needs to be noted that shortening the period of progressive Mtb growth by the equivalent of one Mtb doubling time (28 h) would enable a vaccine to reduce the level of stationary infection by ‫ف‬ 50%. The finding that the pathogen grew at the same rate in immunized and naive mice for the first 12-15 d of infection is in accordance with results obtained with guinea pigs (18) and mice (19). The reason for the exceptionally long delay in immunized, as well as naive, mice before anti-Mtb immunity is expressed in the lungs remains unknown.…”

“…Because the ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and Ag85B 240-254 peptides are Class II (IA b ) presented, it is reasonable to conclude that the cells that made IFN-␥ in response to them were CD4 T cells. This was confirmed by the results of an Elispot assay performed with lung cell suspensions magnetically depleted of Ն 90% CD4 cells.…”

Vaccinated Mice Remain More Susceptible to Mycobacterium tuberculosis Infection Initiated via the Respiratory Route than via the Intravenous Route

“…The levels of lung protection afforded mice against M. tuberculosis challenge infection by BCG vaccination as shown by this study are similar to those shown previously by others for mice (4) and guinea pigs (9). The common finding has been that vaccination enables the host to reduce the level of lung infection but not to resolve it.…”

Temporal Development of Resistance to Pulmonary Tuberculosis in Swiss Albino Mice

“…Ribi et al confirmed these findings, adding that significant pulmonary protection, greater than that obtained with living BCG, was also achieved by intravenous injection of oil in water emulsions of mycobacterial cell walls (9,10). Smith et al found little difference in the response of BCG-vaccinated and unvaccinated mice to virulent human respiratory infection, although the numbers of bacilli recovered from lungs and spleens in immunized mice were smaller at certain intervals of time after infection (11).…”