ArticleThe Journal of infectious diseases2020
Bacillus Calmette-Guérin Overexpressing an Endogenous Stimulator of Interferon Genes Agonist Provides Enhanced Protection Against Pulmonary Tuberculosis.
Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 39 citations in OpenAlex.
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- Type I interferons in tuberculosis pathogenesis and prevention.Trends in microbiology · 2026Review
- Increased vaccine efficacy against tuberculosis with a recombinant BCG overexpressing the STING agonist cyclic di-AMP.bioRxiv : the preprint server for biology · 2025Article
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Impact and applications of cyclic di-GMP second messenger signaling in biotechnology and medicine.Sustainable microbiology · 2025Review
- Article
- Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Mycobacterial Nucleic Acids Modulate Host Innate Immune Responses.Journal of infectious disease and therapy · 2024Article
- Improved bladder cancer antitumor efficacy with a recombinant BCG that releases a STING agonist.bioRxiv : the preprint server for biology · 2023Article
- Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023Review
- Review
- Fighting Tuberculosis: In Search of a BCG Replacement.Microorganisms · 2022Review
- Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis.Biomedicines · 2022Review
- Recombinant BCG to Enhance Its Immunomodulatory Activities.Vaccines · 2022Review
- TheMolecular therapy. Nucleic acids · 2022Article
- Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer.Nature communications · 2022Article
- BCG invokes superior STING-mediated innate immune response over radiotherapy in a carcinogen murine model of urothelial cancer.The Journal of pathology · 2022Article
- c-di-AMP Accumulation Regulates Growth, Metabolism, and Immunogenicity ofFrontiers in microbiology · 2022Article
- Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses AgainstFrontiers in cellular and infection microbiology · 2022Article
- Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection againstFrontiers in immunology · 2022Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundStimulator of interferon genes (STING) is a key cytosolic receptor for small nucleotides and plays a key role in anticancer and antiviral immunity. Cyclic dinucleotide STING agonists may comprise a novel class of vaccine adjuvants capable of inducing cellular immune responses and protective efficacy against intracellular pathogens.
methodsWe generated a recombinant Bacillus Calmette-Guérin ([BCG] BCG-disA-OE) that overexpresses the endogenous mycobacterial diadenylate cyclase gene and releases high levels of the STING agonist bis-(3'-5')-cyclic dimeric adenosine monophosphate (c-di-AMP). We used a 24-week guinea pig vaccination-Mycobacterium tuberculosis (M.tb.) challenge model to test the protective efficacy of BCG-disA-OE versus wild-type BCG and measured lung weights, pathology scores, and M.tb. organ colony-forming unit (CFU) counts.
resultsBCG-disA-OE elicited significantly stronger tumor necrosis factor-α, interleukin (IL)-6, IL-1β, interferon (IFN) regulatory factor 3, and IFN-β levels than BCG-wild type (WT) in vitro in murine macrophages. In vivo in guinea pigs, we found that BCG-disA-OE reduced lung weights, pathology scores, and M.tb. CFU counts in lungs by 28% (P < .05), 34%, and 2.0 log10 CFU units (P < .05) compared with BCG-WT, respectively.
conclusionsWe report a strategy of delivering a STING agonist from within live BCG. Overproduction of the STING agonist c-di-AMP significantly enhanced the protective efficacy of BCG against pulmonary and extrapulmonary tuberculosis. Our findings support the development of BCG-vectored STING agonists as a tuberculosis vaccine strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.