ArticlebioRxiv : the preprint server for biology2025
Leveraging a synthetic biology approach to enhance BCG-mediated expansion of Vγ9Vδ2 T cells.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
There is an urgent need to develop a more efficacious anti-tuberculosis vaccine as the current live-attenuated vaccine strain BCG fails to prevent pulmonary infection in adults. Our long-term goal is to test whether increasing the immunogenicity of BCG will improve vaccine effectiveness while maintaining its proven safety profile. In this study, we leverage a synthetic biology approach to engineer BCG to produce more (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), a phosphoantigen produced as an intermediate of bacterial-but not host-isoprenoid biosynthesis via the methylerythritol phosphate (MEP) pathway. Importantly, HMBPP strongly activates and expands Vγ9Vδ2 T cells, which are unique to higher-order primates and protect against
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