Non-Specific Effects of Bacillus Calmette-Guérin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Trunk, Gerhard; Davidović, Maša; Bohlius, Julia (2023). Non-Specific Effects of Bacillus Calmette-Guérin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Vaccines, 11(1), p. 121. MDPI 10.3390/vaccines11010121

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BACKGROUND

Vaccines induce antigen-specific immunity, which provides long-lived protection from the target pathogen. Trials from areas with high incidence rates for infectious diseases indicated that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) induces in addition non-specific immunity against various pathogens and thereby reduces overall mortality more than would have been expected by just protecting from tuberculosis. Although recent trials produced conflicting results, it was suggested that BCG might protect from non-tuberculosis respiratory infections and could be used to bridge the time until a specific vaccine against novel respiratory diseases like COVID-19 is available.

METHODS

We performed a systematic search for randomized controlled trials (RCTs) published between 2011 and December 9th, 2022, providing evidence about non-specific effects after BCG vaccination, assessed their potential for bias, and meta-analyzed relevant clinical outcomes. We excluded RCTs investigating vaccination with an additional vaccine unless outcomes from a follow-up period before the second vaccination were reported.

RESULTS

Our search identified 16 RCTs including 34,197 participants. Vaccination with BCG caused an estimated 44% decrease in risk for respiratory infections (hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.82) with substantial heterogeneity between trials (I2 = 77%). There was evidence for a protective effect on all-cause mortality of 21% if follow-up was restricted to one year (HR 0.79, 95% CI 0.64-0.99). We did not find evidence for an effect when we considered longer follow-up (HR 0.88, 95% CI 0.75-1.03). Infection-related mortality after BCG vaccination was reduced by 33% (HR 0.67; 95% CI 0.46-0.99), mortality for sepsis by 38% (HR 0.62, 95% CI 0.41-0.93). There was no evidence for a protective effect of BCG vaccination on infections of any origin (HR 0.84, 95% CI 0.71-1.00), COVID-19 (HR 0.88, 95% CI 0.68-1.14), sepsis (HR 0.78, 95% CI 0.55-1.10) or hospitalization (HR 1.01, 95% CI 0.91-1.11).

CONCLUSIONS

According to these results, depending on the setting, vaccination with BCG provides time-limited partial protection against non-tuberculosis respiratory infections and may reduce mortality. These findings underline BCG's potential (1) in pandemic preparedness against novel pathogens especially in developing countries with established BCG vaccination programs but limited access to specific vaccines; (2) in reducing microbial infections, antimicrobial prescriptions and thus the development of antimicrobial resistance. There is a need for additional RCTs to clarify the circumstances under which BCG's non-specific protective effects are mediated.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Bohlius, Julia Friederike

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

23 Jan 2023 10:02

Last Modified:

25 Mar 2024 09:19

Publisher DOI:

10.3390/vaccines11010121

PubMed ID:

36679966

Uncontrolled Keywords:

BCG COVID-19 non-specific effects pandemic preparedness respiratory infection trained immunity vaccine

BORIS DOI:

10.48350/177753

URI:

https://boris.unibe.ch/id/eprint/177753

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