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

View ORCID ProfileBhagwati Khatri, James Keeble, Belinda Dagg, Daryan A. Kaveh, Philip J. Hogarth, Mei Mei Ho
doi: https://doi.org/10.1101/2020.10.21.349373
Bhagwati Khatri
1Bacteriology Division, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, United Kingdom
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  • ORCID record for Bhagwati Khatri
  • For correspondence: bhagwati.khatri@nibsc.org
James Keeble
1Bacteriology Division, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, United Kingdom
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Belinda Dagg
1Bacteriology Division, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, United Kingdom
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Daryan A. Kaveh
2Department of Bacteriology, Animal and Plant Health Agency, Addlestone, Surrey, KT15 3NB, United Kingdom
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Philip J. Hogarth
2Department of Bacteriology, Animal and Plant Health Agency, Addlestone, Surrey, KT15 3NB, United Kingdom
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Mei Mei Ho
1Bacteriology Division, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, United Kingdom
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Abstract

In this study, 2 strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3×105 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 3×105 – 3000 CFU (BALB/c) and 3×105-300 CFU (CB6F1). Whereas, both strains of mice when infected with H37Rv, significant protection was seen in BCG doses at 3×105 - 300 CFU. Immunological evaluation revealed interesting results; i) both strains of mice demonstrated a significant increase in the frequencies of BCG-specific IFNγ+ IL2+ TNFα+ CD4 T cells in the BCG doses at 3×105 – 3000 CFU (BALB/c) and 3×105 - 300 CFU (CB6F1); ii) secretion of IL2 and IFNγ 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.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 21, 2020.
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Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878
Bhagwati Khatri, James Keeble, Belinda Dagg, Daryan A. Kaveh, Philip J. Hogarth, Mei Mei Ho
bioRxiv 2020.10.21.349373; doi: https://doi.org/10.1101/2020.10.21.349373
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Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878
Bhagwati Khatri, James Keeble, Belinda Dagg, Daryan A. Kaveh, Philip J. Hogarth, Mei Mei Ho
bioRxiv 2020.10.21.349373; doi: https://doi.org/10.1101/2020.10.21.349373

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