Live Attenuated Vaccines Against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria

Overview

Journal Vaccines (Basel)

Date 2024 May 25

PMID 38793781

Authors

Raja Veerapandian

Shrikanth S Gadad

Chinnaswamy Jagannath

Subramanian Dhandayuthapani

Affiliations

Soon will be listed here.

Abstract

Tuberculosis (TB), a chronic infectious disease affecting humans, causes over 1.3 million deaths per year throughout the world. The current preventive vaccine BCG provides protection against childhood TB, but it fails to protect against pulmonary TB. Multiple candidates have been evaluated to either replace or boost the efficacy of the BCG vaccine, including subunit protein, DNA, virus vector-based vaccines, etc., most of which provide only short-term immunity. Several live attenuated vaccines derived from () and BCG have also been developed to induce long-term immunity. Since mediates its virulence through multiple secreted proteins, these proteins have been targeted to produce attenuated but immunogenic vaccines. In this review, we discuss the characteristics and prospects of live attenuated vaccines generated by targeting the disruption of the genes encoding secretory mycobacterial proteins.

Citing Articles

Long non-coding RNA transcripts in -host interactions.

Vijayaraghavan M, Gadad S, Dhandayuthapani S Noncoding RNA Res. 2025; 11:281-293.

PMID: 39926616 PMC: 11803167. DOI: 10.1016/j.ncrna.2024.12.005.

References

Zhao X, Zhu L, Chang Q, Jiang C, You Y, Luo T . C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation. J Biol Chem. 2014; 289(43):30052-62. PMC: 4208012. DOI: 10.1074/jbc.M114.588574. View

Netea M, Joosten L, Latz E, Mills K, Natoli G, Stunnenberg H . Trained immunity: A program of innate immune memory in health and disease. Science. 2016; 352(6284):aaf1098. PMC: 5087274. DOI: 10.1126/science.aaf1098. View

Abdallah A, Savage N, van Zon M, Wilson L, Vandenbroucke-Grauls C, van der Wel N . The ESX-5 secretion system of Mycobacterium marinum modulates the macrophage response. J Immunol. 2008; 181(10):7166-75. DOI: 10.4049/jimmunol.181.10.7166. View

Wang J, Ge P, Qiang L, Tian F, Zhao D, Chai Q . The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation. Nat Commun. 2017; 8(1):244. PMC: 5557760. DOI: 10.1038/s41467-017-00279-z. View

Kim K, An D, Song J, Yoon J, Kim H, Yoon H . Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc Natl Acad Sci U S A. 2012; 109(20):7729-34. PMC: 3356628. DOI: 10.1073/pnas.1120251109. 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

Cosma C, Klein K, Kim R, Beery D, Ramakrishnan L . Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival. Infect Immun. 2006; 74(6):3125-33. PMC: 1479242. DOI: 10.1128/IAI.02061-05. View

Lewis K, Liao R, Guinn K, Hickey M, Smith S, Behr M . Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation. J Infect Dis. 2003; 187(1):117-23. PMC: 1458498. DOI: 10.1086/345862. View

Wu F, Liu Y, Zhang H, Jiang H, Cheng L, Guo S . Global Profiling of PknG Interactions Using a Human Proteome Microarray Reveals Novel Connections with CypA. Proteomics. 2018; 18(23):e1800265. DOI: 10.1002/pmic.201800265. View

10.

Abdallah A, Gey van Pittius N, Champion P, Cox J, Luirink J, Vandenbroucke-Grauls C . Type VII secretion--mycobacteria show the way. Nat Rev Microbiol. 2007; 5(11):883-91. DOI: 10.1038/nrmicro1773. View

11.

Tiwari S, Dutt T, Chen B, Chen M, Kim J, Dai A . BCG-Prime and boost with Esx-5 secretion system deletion mutant leads to better protection against clinical strains of Mycobacterium tuberculosis. Vaccine. 2020; 38(45):7156-7165. PMC: 7755135. DOI: 10.1016/j.vaccine.2020.08.004. View

12.

Larsen S, Erasmus J, Reese V, Pecor T, Archer J, Kandahar A . An RNA-Based Vaccine Platform for Use against . Vaccines (Basel). 2023; 11(1). PMC: 9862644. DOI: 10.3390/vaccines11010130. View

13.

Fishbein S, Wyk N, Warren R, Sampson S . Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity. Mol Microbiol. 2015; 96(5):901-16. DOI: 10.1111/mmi.12981. View

14.

Saikolappan S, Estrella J, Sasindran S, Khan A, Armitige L, Jagannath C . The fbpA/sapM double knock out strain of Mycobacterium tuberculosis is highly attenuated and immunogenic in macrophages. PLoS One. 2012; 7(5):e36198. PMC: 3344844. DOI: 10.1371/journal.pone.0036198. View

15.

Pradhan G, Shrivastva R, Mukhopadhyay S . Mycobacterial PknG Targets the Rab7l1 Signaling Pathway To Inhibit Phagosome-Lysosome Fusion. J Immunol. 2018; 201(5):1421-1433. DOI: 10.4049/jimmunol.1800530. View

16.

Dey S, Lane J, Lee R, Rubin E, Sacchettini J . Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase . Biochemistry. 2010; 49(31):6746-60. PMC: 3503319. DOI: 10.1021/bi902097j. View

17.

Germic N, Frangez Z, Yousefi S, Simon H . Regulation of the innate immune system by autophagy: monocytes, macrophages, dendritic cells and antigen presentation. Cell Death Differ. 2019; 26(4):715-727. PMC: 6460400. DOI: 10.1038/s41418-019-0297-6. View

18.

Roche C, Smith A, Lindsey D, Meher A, Schluns K, Arora A . The ΔfbpA attenuated candidate vaccine from Mycobacterium tuberculosis, H37Rv primes for a stronger T-bet dependent Th1 immunity in mice. Tuberculosis (Edinb). 2011; 91 Suppl 1:S96-104. PMC: 3248993. DOI: 10.1016/j.tube.2011.10.018. View

19.

Gengenbacher M, Nieuwenhuizen N, Vogelzang A, Liu H, Kaiser P, Schuerer S . Deletion of nuoG from the Vaccine Candidate Mycobacterium bovis BCG ΔureC::hly Improves Protection against Tuberculosis. mBio. 2016; 7(3). PMC: 4895111. DOI: 10.1128/mBio.00679-16. View

20.

Porcelli S, Morita C, Brenner M . CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen. Nature. 1992; 360(6404):593-7. DOI: 10.1038/360593a0. View