How cell-free processes could speed up vaccine development

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Developed by Vaxcyte in San Carlos, California, VAX-24 induces an immune reaction to Streptococcus pneumoniae by exposing the body to bacterial sugars linked to a carrier protein — known as a protein conjugate vaccine. Market-leading PREVNAR-20, produced by US pharmaceutical giant Pfizer, has a similar design. But whereas PREVNAR-20’s protein conjugates are purified from bacteria, those in VAX-24 are built biochemically.

Vaxcyte is one of a growing number of biomanufacturing firms embracing this cell-free biosynthesis strategy. Instead of relying on yeast or bacteria to make biomolecules, the approach strips away all the components of a cell that make it ‘alive’ — the long strings of DNA, the complex origami of the endoplasmic reticulum and even the bulwark of the cell membrane — and freeze-dries what remains. Scientists can then rehydrate the dried material with water and add nucleic acids to program the molecular machinery to make an infinite array of proteins on demand.

Tobias Erb, a microbial physiologist at the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany, likens the process to using a commercial cake mix: just add water and bake. To Michael Jewett, a chemical and biological engineer at Northwestern University in Evanston, Illinois, the strategy is more like popping open the bonnet of a car, removing the engine and repurposing it to power a drill.

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