ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Metabolic engineering of Salmonella vaccine bacteria to boost human Vγ2Vδ2 T cell immunity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune responses that correlate with safety and may be associated to therapy potential.Journal for immunotherapy of cancer · 2023Article
- Phenotypic and functional characterization of pharmacologically expanded Vγ9Vδ2 T cells in pigtail macaques.iScience · 2023Article
- BCG-activation of leukocytes is sufficient for the generation of donor-independent innate anti-tumor NK and γδ T-cells that can be further expandedOncoimmunology · 2023Article
- Bacillus Calmette-Guerin (BCG) induces superior anti-tumour responses by Vδ2+ T cells compared with the aminobisphosphonate drug zoledronic acid.Clinical and experimental immunology · 2022Article
- Releasing the restraints of Vγ9Vδ2 T-cells in cancer immunotherapy.Frontiers in immunology · 2022Article
- Role of Vγ9vδ2 T lymphocytes in infectious diseases.Frontiers in immunology · 2022Review
- Article
- Immuno-antibiotics: targeting microbial metabolic pathways sensed by unconventional T cells.Immunotherapy advances · 2021Review
- The role of the innate immune system on pulmonary infections.Biological chemistry · 2019Review
- Emerging role of γδ T cells in vaccine-mediated protection from infectious diseases.Clinical & translational immunology · 2019Review
- Improving the Efficiency of Vγ9Vδ2 T-Cell Immunotherapy in Cancer.Frontiers in immunology · 2018Review
- Unconventional Human T Cells Accumulate at the Site of Infection in Response to Microbial Ligands and Induce Local Tissue Remodeling.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Early innate responses to pathogens: pattern recognition by unconventional human T-cells.Current opinion in immunology · 2015Review
- Resistance-resistant antibiotics.Trends in pharmacological sciences · 2014Review
- Salmonella-how a metabolic generalist adopts an intracellular lifestyle during infection.Frontiers in cellular and infection microbiology · 2014Review
- Pathogen-Specific Immune Fingerprints during Acute Infection: The Diagnostic Potential of Human γδ T-Cells.Frontiers in immunology · 2014Review
- How to Train Your Dragon: Harnessing Gamma Delta T Cells Antiviral Functions and Trained Immunity in a Pandemic Era.Frontiers in immunologyReview
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Human Vγ2Vδ2 T cells monitor isoprenoid metabolism by recognizing foreign (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a metabolite in the 2-C-methyl-D-erythritol-4-phosphate pathway used by most eubacteria and apicomplexan parasites, and self isopentenyl pyrophosphate, a metabolite in the mevalonate pathway used by humans. Whereas microbial infections elicit prolonged expansion of memory Vγ2Vδ2 T cells, immunization with prenyl pyrophosphates or aminobisphosphonates elicit short-term Vγ2Vδ2 expansion with rapid anergy and deletion upon subsequent immunizations. We hypothesized that a live, attenuated bacterial vaccine that overproduces HMBPP would elicit long-lasting Vγ2Vδ2 T cell immunity by mimicking a natural infection. Therefore, we metabolically engineered the avirulent aroA(-) Salmonella enterica serovar Typhimurium SL7207 strain by deleting the gene for LytB (the downstream enzyme from HMBPP) and functionally complementing for this loss with genes encoding mevalonate pathway enzymes. LytB(-) Salmonella SL7207 had high HMBPP levels, infected human cells as efficiently as did the wild-type bacteria, and stimulated large ex vivo expansions of Vγ2Vδ2 T cells from human donors. Importantly, vaccination of a rhesus monkey with live lytB(-) Salmonella SL7207 stimulated a prolonged expansion of Vγ2Vδ2 T cells without significant side effects or anergy induction. These studies provide proof-of-principle that metabolic engineering can be used to derive live bacterial vaccines that boost Vγ2Vδ2 T cell immunity. Similar engineering of metabolic pathways to produce lipid Ags or B vitamin metabolite Ags could be used to derive live bacterial vaccine for other unconventional T cells that recognize nonpeptide Ags.
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Registered trials
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