Revisiting Bacille Calmette-Guérin revaccination strategies: timing of immunization, Mycobacterium tuberculosis and non-tuberculous mycobacteria infections, strain potency and standardization of randomized controlled trials

Abstract

The persistent threat of tuberculosis (TB) on a global scale hasprompted a reevaluation of preventive strategies, with a particular focus onthe Bacille Calmette-Guérin (BCG) vaccine's role in revaccination. Theresurgence underscores an urgent need for enhanced measures, prompting acritical examination of BCG revaccination strategies. Drawing from the researchof Paulo Cesar Pereira dos Santos and a synthesis of randomized controlledtrials (RCTs), this review identifies key considerations for refining BCGrevaccination's efficacy against Mycobacterium tuberculosis (MTB) andTB. The main body of this review integrates four principal domains essentialfor optimizing BCG revaccination: the timing of revaccination, the assessmentof various BCG strains, the evaluation of the vaccine's effectiveness on MTBand non-tuberculous mycobacteria (NTM) strains, and the enhancement of RCTmethodologies. Determining the optimal revaccination timing is paramount forbolstering immunity, especially in regions with high TB prevalence. Theanalysis of different BCG strains provides insights into strain-specificimmunogenicity, informing vaccine deployment strategies. Additionally, understanding the vaccine's impact on a range of mycobacterial infections iscrucial for its broader application in various microbial contexts. The reviewemphasizes the refinement of RCT designs to ensure robust and consistentoutcomes, facilitating the reproducibility of results in diverse settings. Itproposes a strategy that not only suggests modifications to revaccinationpractices to increase global TB prevention effectiveness but also calls forcontinuous research to improve BCG revaccination methodologies. The paperadvocates for a standardized, evidence-driven approach to global TB preventionthat takes into account regional epidemiological differences. In conclusion, this review significantly contributes to the discourse on TB prevention, advocating for evidence-based, standardized approaches that could potentiallytransform the role of BCG revaccination in global TB prevention efforts. Thefindings support current initiatives aimed at developing policies based onsolid evidence, ensuring the scientific integrity and practical relevance ofBCG revaccination strategies.

Keywords

Bacille Calmette-Guérin / efficacy / non-tuberculous mycobacteria / randomized controlled trial / tuberculosis

References

[1] BehrMA, SmallPM. A historical and molecular phylogeny of BCG strains. Vaccine. 1999;17(7-8):915-922.

[2] RodriguesLC, Pereira SM, CunhaSS, et al. Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial. Lancet. 2005;366(9493):1290-1295.

[3] Dos SantosPCP, Messina NL, de OliveiraRD, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial. Lancet Infect Dis. Published online: February 26, 2024:S1473-3099(23)00818-6. Online ahead of print

[4] LiL, YangL, ZhuangL, Ye Z, ZhaoW, GongW. From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning. Mil Med Res. 2023;10(1):58.

[5] AndersenP, Doherty TM. The success and failure of BCG—implications for a novel tuberculosis vaccine. Nat Rev Microbiol. 2005;3(8):656-662.

[6] NemesE, Geldenhuys H, RozotV, et al. Prevention of M. tuberculosis infection with H4:iC31 vaccine or BCG revaccination. New Engl J Med. 2018;379(2):138-149.

[7] BarretoML, Pereira SM, PilgerD, et al. Evidence of an effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: second report of the BCG-REVAC cluster-randomised trial. Vaccine. 2011;29(31):4875-4877.

[8] GlynnJR, Fielding K, MzembeT, et al. BCG re-vaccination in Malawi: 30-year follow-up of a large, randomised, double-blind, placebo-controlled trial. Lancet Global Health. 2021;9(10):e1451-e1459.

[9] GongW, DuJ. Optimising the vaccine strategy of BCG, ChAdOx1 85A, and MVA85A for tuberculosis control. Lancet Infect Dis. 2024;24(3):224-226. Comment

[10] GongW, DuJ, ZhuangL, Wu X. Exploring BCG vaccination as a novel approach to prevent recurrent herpes labialis. EClinicalMedicine. 2023;65:102279.

[11] GongW, DuJ. Excluding participants with mycobacteria infections from clinical trials: a critical consideration in evaluating the efficacy of BCG against COVID-19. J Korean Med Sci. 2023;38(42):e343.

[12] SulimanS, Geldenhuys H, JohnsonJL, et al. Bacillus Calmette-Guérin (BCG) revaccination of adults with latent Mycobacterium tuberculosis infection induces long-lived BCG-Reactive NK cell responses. J Immunol. 2016;197(4):1100-1110.

[13] FinePE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346(8986):1339-1345.

[14] BierrenbachAL, CunhaSS, BarretoML, et al. Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage. Pan Am J Public Health. 2003;13(5):285-293.

[15] RitzN, Hanekom WA, Robins-BrowneR, BrittonWJ, CurtisN. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008;32(5):821-841.

[16] RitzN, DuttaB, DonathS, et al. The influence of Bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial. Am J Respir Crit Care Med. 2012;185(2):213-222.

[17] AspatwarA, GongW, WangS, Wu X, ParkkilaS. Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic. Int Rev Immunol. 2022;41(2):283-296.

[18] HarboeM, NagaiS, PatarroyoME, Torres ML, RamirezC, CruzN. Properties of proteins MPB64, MPB70, and MPB80 of Mycobacterium bovis BCG. Infect Immun. 1986;52(1):293-302.

[19] AbdallahAM, Hill-Cawthorne GA, OttoTD, et al. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations. Sci Rep. 2015;5:15443.

[20] VelayuthamB, Thiruvengadam K, KumaranPP, WatsonB, Rajendran K, PadmapriyadarsiniC. Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease. Indian J Med Res. 2023;157(2&3):152-159.

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2024 2024 The Authors. Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.