title: Potency testing of BCG vaccines on white mice: influence of variables on survival time, lung findings and vaccine assessment.
abstract: In protection tests on white mice vaccinated with BCG vaccine and challenged with a pathogenic strain of Mycobacterium bovis, the survival times are considerably altered by several variables. In the strains of mice used mainly in this study (NMRI and Albany), the median survival time of a group was roughly doubled in the sensitive range of the test system either by a twofold increase in the immunization period, a threefold decrease in the challenge dose or a 100-fold or less increase in the vaccine dose. The shape of the survival curve of an animal group depends on the median survival time achieved. The Gaussian distributions (sum curves) of the logarithms of the individual survival times are near linearity and parallelity in groups of animals which either survive for short or very long periods. In an intermediate range, however, the survival curves show a flatter and sometimes S-shaped course. This intermediate range of survival corresponds to the time at which the lung findings shift from acute to chronic. The occurrence of acute or chronic findings depends on the individual survival time after challenge. The autopsies show that both findings are equally frequent approximately equal to 35 days after challenge. Individual survival times should be evaluated by non-parametric methods due to their non-normal (bimodal) distribution. Evaluation of the gross lung findings supports these results but is, however, less efficient. The discriminating power of the test system can be altered by changes in any of the variables and is best when animal groups attaining less than 20 days median survival time are compared with groups attaining greater than 30 days. A twofold increase in the median survival time generally provides evidence of significance that may already be obtained 30 days after challenge. With a vaccination-challenge interval of 21 days or more, a 50 microliter vaccine dose generally induces a significant increase in the survival times of the vaccinated animals versus non-vaccinated controls. With increasing immunization periods (vaccination-challenge interval), however, a difference in the efficacy of several vaccines or vaccine doses will be evened out.
authors.affiliation: Behringwerke AG, Marburg, FRG.
authors.forename: H
authors.initials: H
authors.lastname: Freudenstein
authors.forename: E
authors.initials: E
authors.lastname: Weinmann
authors.forename: I
authors.initials: I
authors.lastname: Hill
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000592:standards*; D005260:Female; D007115:Immunization Schedule; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D012737:Sex Factors; D013997:Time Factors; D014376:Tuberculosis / Q000473:pathology / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001500:BCG Vaccine