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Science Studies Describe Role for Microbiome-Derived Immunity, Platform to Develop Flavivirus Vaccines

Using a new CRISPR-Cas9-based genome-deletion tool, a team led by Stanford University investigators has uncovered a role for microbiome-derived molecules in immunity. In order to better understand the role of the hundreds of molecules produced by gut microbiota that enter circulation, the scientists developed a knockout system for the gut bacterium Clostridium. As detailed in this week's Science, the method was used to produce knockout strains of the model commensal organism Clostridium sporogenes that are unable to unable to synthesize branched short-chain fatty acids. When these strains were colonized in germ-free mice, the animals showed dysregulation in immunoglobulin A production.

By genetically modifying a strain of flavivirus that only infects insects, a University of Queensland-led team has developed a platform for the development of vaccines and diagnostics for flavivirus infections such as Zika and dengue. The insect-specific flavivirus, called Binjari virus, is extremely tolerant for exchange of its structural protein genes with those of pathogenic vertebrate-infecting flaviviruses, the scientists write in Science Translational Medicine. When Binjari viruses were engineered to contain genes from Zika or West Nile, they reproduced rapidly in mosquito cells but cannot infect vertebrate cells. The findings suggest that modified Binjari viruses could be used to generate chimeric flavivirus particles with low biocontainment requirements.