Journal article

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

Asimenia Angelidou, Maria-Giulia Conti, Joann Diray-Arce, Christine S Benn, Frank Shann, Mihai G Netea, Mark Liu, Lakshmi Prasad Potluri, Guzman Sanchez-Schmitz, Robert Husson, Al Ozonoff, Beate Kampmann, Simon Daniel van Haren, Ofer Levy

Vaccine | ELSEVIER SCI LTD | Published : 2020

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: Up..

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Grants

Awarded by National Institute of Allergy and Infectious Diseases (NIAID)


Awarded by Human Immunology Project Consortium (HIPC)


Awarded by Danish National Research Foundation


Awarded by UK Research and Innovation (UKRI)


Funding Acknowledgements

This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (NIAID), including those on Molecular Mechanisms of Combination Adjuvants (grant number U01Al124284 to SvH) and the Human Immunology Project Consortium (HIPC; grant number U19A1118608). AA received the Marshall Klaus Perinatal Research Award from the American Academy of Pediatrics. MGC was sponsored by Sapienza University of Rome and was a recipient of the Admeto Pettinnari e Paolo Andreini graduate scholarship for specialization courses in Italy and abroad. CSB received funding from the Danish National Research Foundation (DNRF108). MGN was supported by a Spinoza grant of the Netherlands Organization for Scientific Research. BK is funded by UK Research and Innovation (UKRI) (grant number MC_UP_A900/1122; MR/K011944/1) and is a co-investigator of HIPC. AA, AO, GSS, OL, and SvH were in part supported by the Precision Vaccines Program at Boston Children's Hospital.