Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878

Abstract

In this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette Guerin (BCG) Danish doses from 300,000 to 30 CFU/mouse, followed by either immunogenicity evaluation or aerosol infection with Mycobacterium tuberculosis (a laboratory strain H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 300,000 to 3000 CFU (BALB/c) and 300,000 to 300 CFU (CB6F1). Whereas, both strains of mice when infected with H37Rv, significant protection was seen in BCG doses at 300,000 to 300 CFU. Immunological evaluation revealed interesting results; i) both strains of mice demonstrated a significant increase in the frequencies of BCG specific IFN[gamma]+ IL2+ TNF[alpha]+ CD4 T cells in the BCG doses at 300,000 to 3000 CFU (BALB/c) and 300,000 to 300 CFU (CB6F1); ii) secretion of IL2 and IFN[gamma]; were correlated with the bacterial burden in the lungs of HN878 infected CB6F1 mice. The study demonstrated a BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight index) is protective in both strains of mice and the use of a virulent clinical isolate in testing new tuberculosis vaccine/advancing research is recommended.

BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

“…First, unlike our previous report, we found that wild-type BCG conferred protection against Mtb M2 infection 31 . Potential explanations include the following: (1) the inoculation dose of BCG was different between the work of Gröschel et al 59 and the current study, as it has been reported that the efficacy and immunogenicity were differentially affected according to the BCG dose. (2) This could also be the result of using different parental BCG strains (ATCC 35734 in this study versus BCG Pasteur 1173P2 kindly provided by Dr Brosch).…”