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Review
. 2020 Nov:36:57-64.
doi: 10.1016/j.prrv.2020.08.004. Epub 2020 Aug 20.

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects

Nora Fritschi  1 , Nigel Curtis  2 , Nicole Ritz  3
Affiliations
Review

Bacille Calmette Guérin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects

Nora Fritschi et al. Paediatr Respir Rev. 2020 Nov.

Abstract

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.

Keywords: Active TB; COVID-19; Cross-protective; Latent TB; SARS-CoV-2; Trained immunity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Summary of the specific, cross-mycobacterial and off-target effects of BCG relevant to children.
Fig. 2
Fig. 2
Novel TB vaccine strategies with example vaccines. Only vaccines that are in (or registered for) phase II or III trials are included. The colours around vaccines denote trials that have shown improved protection (green), no improvement (orange), or not discussed/no results available (yellow). H4:IC31: fusion protein of antigens 85B and TB10.4 with IC31 adjuvant H56:IC31: fusion protein of antigens 85B, ESAT-6 and Rv2660c with IC31 adjuvant M72/AS01E: fusion protein of antigen 32A and 39A with AS01E adjuvant MVA85: modified vaccinia Ankara 85A TB/FLU-04L: influenza A vectored vaccine expressing the antigens 85A and ESAT-6 MTBVAC: live attenuated M. tuberculosis strain (Euro-American lineage 4) with deletion mutations in the virulence genes phoP and fadD26 VPM1002C: live attenduated M. bovis BCG-Prague (rBCGΔureC:Hly) DAR-901: heat-killed, fragmented M. tuberculosis cultured under stress conditions MIP: heat-killed Mycobacterium indicus pranii a non-pathogenic, non-tuberculous mycobacterium approved in India as a leprosy vaccine M. vaccae: heat-killed Mycobacterium vaccae a non-pathogenic, non-tuberculous mycobacterium.
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References

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