ArticleScientific reports2016
Loss of Lipid Virulence Factors Reduces the Efficacy of the BCG Vaccine.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- A BCG-boosting subunit vaccine RS2/DMI induces Th1-polarized immunity by targeting RD6 and secretory antigens of Mycobacterium tuberculosis.Archives of microbiology · 2025Article
- Mycobacterial phthiocerol dimycocerosate induces Galectin-3 upregulation to impair proinflammatory responses and favor immune evasion.International journal of biological macromolecules · 2025Article
- Comparative transcriptomic signatures of virulent and attenuatedFrontiers in cellular and infection microbiology · 2025Article
- Propionate prevents loss of the PDIM virulence lipid in Mycobacterium tuberculosis.Nature microbiology · 2024Article
- Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.Vaccines · 2024Review
- The PDIM paradox ofbioRxiv : the preprint server for biology · 2023Article
- Mapping the phylogeny and lineage history of geographically distinct BCG vaccine strains.Microbial genomics · 2023Article
- Selective delipidation of Mycobacterium bovis BCG retains antitumor efficacy against non-muscle invasive bladder cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur.Memorias do Instituto Oswaldo Cruz · 2023Article
- Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract.Frontiers in immunology · 2023Article
- Article
- RNA Microarray-Based Comparison of Innate Immune Phenotypes between Human THP-1 Macrophages Stimulated with Two BCG Strains.International journal of molecular sciences · 2022Article
- Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-γ/IL-17 release in bladder cancer treatment.Oncoimmunology · 2022Article
- Article
- In silico comparisons of lipid-related genes between Mycobacterium tuberculosis and BCG vaccine strains.Genetics and molecular biology · 2021Article
- The BCG Vaccine for COVID-19: First Verdict and Future Directions.Frontiers in immunology · 2021Review
- Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins.International journal of molecular sciences · 2020Review
- Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis.BioMed research international · 2020Review
- Tuberculosis Vaccine Development: Progress in Clinical Evaluation.Clinical microbiology reviews · 2019Review
- Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle.BMC genomics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. BCG comprises a number of substrains that exhibit genetic and biochemical differences. Whether and how these differences affect BCG efficacy remain unknown. Compared to other BCG strains, BCG-Japan, -Moreau, and -Glaxo are defective in the production of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs), two lipid virulence factors. To determine if the loss of PDIMs/PGLs affects BCG efficacy, we constructed a PDIM/PGL-deficient strain of BCG-Pasteur by deleting fadD28, and compared virulence, immunogenicity, and protective efficacy in animal models. SCID mouse infection experiments showed that ∆fadD28 was more attenuated than wild type (WT). The ∆fadD28 and WT strains induced equivalent levels of antigen specific IFN-γ by CD4(+) and CD8(+) T cells; however, ∆fadD28 was less effective against Mycobacterium tuberculosis challenge in both BALB/c mice and guinea pigs. These results indicate that the loss of PIDMs/PGLs reduces the virulence and protective efficacy of BCG. Since the loss of PDIMs/PGLs occurs naturally in a subset of BCG strains, it also suggests that these strains may have been over-attenuated, which compromises their effectiveness. Our finding has important implications for current BCG programs and future vaccine development.
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Registered trials
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