A Review of the BCG Vaccine and Other Approaches Toward Tuberculosis Eradication

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2021 Mar 26

PMID 33769193

Citations 14

Authors

Thomas Cho

Christopher Khatchadourian

Huy Nguyen

Yash Dara

Shuna Jung

Vishwanath Venketaraman

Affiliations

Soon will be listed here.

Abstract

Despite aggressive eradication efforts, Tuberculosis (TB) remains a global health burden, one that disproportionally affects poorer, less developed nations. The only vaccine approved for TB, the Bacillus of Calmette and Guérin (BCG) vaccine remains controversial because it's stated efficacy has been cited as anywhere from 0 to 80%. Nevertheless, there have been exciting discoveries about the mechanism of action of the BCG vaccine that suggests it has a role in immunization schedules today. We review recent data suggesting the vaccine imparts protection against both tuberculosis and non-tuberculosis pathogens via a newly discovered immune system called trained immunity. BCG's efficacy also appears to be tied to its affect on granulocytes at the epigenetic and hematopoietic stem cell levels, which we discuss in this article at length. We also write about how the different strains of the BCG vaccine elicit different immune responses, suggesting that certain BCG strains are more immunogenic than others. Finally, our review delves into how the current vaccine is being reformulated to be more efficacious, and track the development of the next generation vaccines against TB.

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References

Wang J, Thorson L, Stokes R, Santosuosso M, Huygen K, Zganiacz A . Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J Immunol. 2004; 173(10):6357-65. DOI: 10.4049/jimmunol.173.10.6357. View

Umemura M, Nishimura H, Hirose K, Matsuguchi T, Yoshikai Y . Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Guérin infection via augmentation of NK and T cytotoxic 1 responses. J Immunol. 2001; 167(2):946-56. DOI: 10.4049/jimmunol.167.2.946. View

Horwitz M, Harth G, Dillon B, Maslesa-Galic S . Commonly administered BCG strains including an evolutionarily early strain and evolutionarily late strains of disparate genealogy induce comparable protective immunity against tuberculosis. Vaccine. 2008; 27(3):441-5. PMC: 2657049. DOI: 10.1016/j.vaccine.2008.10.058. View

Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Eddine A . Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest. 2005; 115(9):2472-9. PMC: 1187936. DOI: 10.1172/JCI24617. View

Gillard P, Yang P, Danilovits M, Su W, Cheng S, Pehme L . Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study. Tuberculosis (Edinb). 2016; 100:118-127. DOI: 10.1016/j.tube.2016.07.005. View

Aagaard C, Hoang T, Izzo A, Billeskov R, Troudt J, Arnett K . Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose. PLoS One. 2009; 4(6):e5930. PMC: 2691953. DOI: 10.1371/journal.pone.0005930. View

Agger E, Rosenkrands I, Olsen A, Hatch G, Williams A, Kritsch C . Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine. 2006; 24(26):5452-60. DOI: 10.1016/j.vaccine.2006.03.072. View

Ekanem A, Oloyede I, Ekrikpo U, Idung A, Edward E . Rate of BCG Immunization in HIV-Exposed Infants in a Selected Primary Health Centre in Southern Nigeria: Implications of No Vaccine Policy for HIV-Positive Infants. J Trop Pediatr. 2020; 67(3). DOI: 10.1093/tropej/fmaa030. View

Gupta A, Ahmad F, Ahmad F, Gupta U, Natarajan M, Katoch V . Protective efficacy of Mycobacterium indicus pranii against tuberculosis and underlying local lung immune responses in guinea pig model. Vaccine. 2012; 30(43):6198-209. DOI: 10.1016/j.vaccine.2012.07.061. View

10.

Dhiman R, Indramohan M, Barnes P, Nayak R, Paidipally P, Rao L . IL-22 produced by human NK cells inhibits growth of Mycobacterium tuberculosis by enhancing phagolysosomal fusion. J Immunol. 2009; 183(10):6639-45. DOI: 10.4049/jimmunol.0902587. View

11.

Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S . Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials. Vaccine. 2017; 35(12):1652-1661. DOI: 10.1016/j.vaccine.2017.01.055. View

12.

Kleinnijenhuis J, Quintin J, Preijers F, Joosten L, Jacobs C, Xavier R . BCG-induced trained immunity in NK cells: Role for non-specific protection to infection. Clin Immunol. 2014; 155(2):213-9. PMC: 5084088. DOI: 10.1016/j.clim.2014.10.005. View

13.

Festjens N, Bogaert P, Batni A, Houthuys E, Plets E, Vanderschaeghe D . Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis. EMBO Mol Med. 2011; 3(4):222-34. PMC: 3377067. DOI: 10.1002/emmm.201000125. View

14.

Singh B, Saqib M, Gupta A, Kumar P, Bhaskar S . Autophagy induction by Mycobacterium indicus pranii promotes Mycobacterium tuberculosis clearance from RAW 264.7 macrophages. PLoS One. 2017; 12(12):e0189606. PMC: 5728553. DOI: 10.1371/journal.pone.0189606. View

15.

Zheng Y, Valdez P, Danilenko D, Hu Y, Sa S, Gong Q . Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med. 2008; 14(3):282-9. DOI: 10.1038/nm1720. View

16.

Sharma S, Katoch K, Sarin R, Balambal R, Jain N, Patel N . Efficacy and Safety of Mycobacterium indicus pranii as an adjunct therapy in Category II pulmonary tuberculosis in a randomized trial. Sci Rep. 2017; 7(1):3354. PMC: 5469738. DOI: 10.1038/s41598-017-03514-1. View

17.

Kumarasamy N, Poongulali S, Beulah F, Akite E, Ayuk L, Bollaerts A . Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial. Medicine (Baltimore). 2018; 97(45):e13120. PMC: 6250513. DOI: 10.1097/MD.0000000000013120. View

18.

Johansen P, Fettelschoss A, Amstutz B, Selchow P, Waeckerle-Men Y, Keller P . Relief from Zmp1-mediated arrest of phagosome maturation is associated with facilitated presentation and enhanced immunogenicity of mycobacterial antigens. Clin Vaccine Immunol. 2011; 18(6):907-13. PMC: 3122614. DOI: 10.1128/CVI.00015-11. View

19.

Sander P, Clark S, Petrera A, Vilaplana C, Meuli M, Selchow P . Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis. Vaccine. 2015; 33(11):1353-9. DOI: 10.1016/j.vaccine.2015.01.058. View

20.

Kiravu A, Osawe S, Happel A, Nundalall T, Wendoh J, Beer S . Bacille Calmette-Guérin Vaccine Strain Modulates the Ontogeny of Both Mycobacterial-Specific and Heterologous T Cell Immunity to Vaccination in Infants. Front Immunol. 2019; 10:2307. PMC: 6793433. DOI: 10.3389/fimmu.2019.02307. View