Dataset Information

Licensed Bacille Calmette-Guerin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.

ABSTRACT:

Background

Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations.

Methods

We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA in vitro with respect to a) viability as measured by colony-forming units (CFU), mycobacterial membrane integrity, and RNA content, and b) cytokine/chemokine production in newborn cord and adult peripheral blood.

Results

Upon culture, relative growth was BCG-USA > JPN ≫ DEN > BUL = IND. BCG-IND and -BUL demonstrated >1000-fold lower growth than BCG-JPN in 7H9 medium and >10-fold lower growth in commercial Middlebrook 7H11 medium. BCG-IND demonstrated significantly decreased membrane integrity, lower RNA content, and weaker IFN-γ inducing activity in whole blood compared to other BCGs. BCG-induced whole blood cytokines differed significantly by age, vaccine formulation and concentration. BCG-induced cytokine production correlated with CFU, suggesting that mycobacterial viability may contribute to BCG-induced immune responses.

Conclusions

Licensed BCG vaccines differ markedly in their content of viable mycobacteria possibly contributing to formulation-dependent activation of innate and adaptive immunity and distinct protective effects.

SUBMITTER: Angelidou A

PROVIDER: S-EPMC7556328 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation.

Angelidou Asimenia A Conti Maria-Giulia MG Diray-Arce Joann J Benn Christine S CS Shann Frank F Netea Mihai G MG Liu Mark M Potluri Lakshmi Prasad LP Sanchez-Schmitz Guzman G Husson Robert R Ozonoff Al A Kampmann Beate B van Haren Simon Daniël SD Levy Ofer O

Vaccine 20200128 9

<h4>Background</h4>Bacille Calmette-Guérin (BCG), the live attenuated tuberculosis vaccine, is manufactured under different conditions across the globe generating formulations that may differ in clinical efficacy. Innate immune recognition of live BCG contributes to immunogenicity suggesting that differences in BCG viability may contribute to divergent activity of licensed formulations.<h4>Methods</h4>We compared BCG-Denmark (DEN), -Japan (JPN), -India (IND), -Bulgaria (BUL) and -USA in vitro wi ...[more]

PMID: 32005538

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