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Synthetic Protein Designed to Boost Covid-19 Vaccines

Jason McLellan and Daniel Wrapp

Jason McLellan, left, and co-author Daniel Wrapp (university of Texas – Austin)

24 July 2020. Researchers in Texas designed a synthetic version of a protein found on Covid-19 viruses that can make it easier to produce more vaccines. A team from the molecular biology lab led by Jason McLellan at University of Texas in Austin describe the protein in yesterday’s issue of the journal Science.

Most of the vaccines protecting against the SARS-CoV-2 coronavirus causing Covid-19 infections target the characteristic protein on the virus’s spikes. When that protein enters human cells, it binds to receptor proteins in the cells and begins an infection process in the lungs and elsewhere in the body. Most Covid-19 vaccines are designed to look like spike proteins to produce an immune response, such as antibodies or T-cells. that block infections from occurring.

In their natural state, however, spike proteins are unstable and difficult to engineer, with many of the early synthetic versions, including those designed in McLellan’s lab, not much more stable than the wild-type proteins. These properties make it difficult to reproduce synthetic proteins in large quantities, and generally slow research and development on Covid-19 vaccines at a time when vaccines are desperately needed worldwide.

McLellan — with UT-Austin co-investigators Ilya Finkelstein, a fellow molecular biologist, and biomedical engineering professor Jennifer Maynard — took a more basic approach to designing a synthetic spike protein. The team analyzed the three-dimensional structure of the spike protein, and tested changes in its chemistry, substituting simple amino acids, called prolines, at various strategic points.

After testing some 100 different protein designs, the researchers identified 26 changes in the spike protein chemistry that add more stability and make it possible to produce the protein in larger quantities. The researchers took the six most effective of these substitutions and combined them in a synthetic version they call HexaPro. Tests in lab cultures show genetic triggers of HexaPro produce 10 times more protein in human cells than earlier synthetic spike protein versions.

Further lab tests also show HexaPro is highly stable. The synthetic protein remains potent after multiple freezing and thawing cycles. In addition, HexaPro can be stored for two days at room temperature, and can withstand temperatures as high as 55 degrees C (131 F). The Bill and Melinda Gates Foundation, a group supporting development of vaccines that can be shipped and stored in lower resource regions, is one of the funders of this research.

“Depending on the type of vaccine,” says McLellan in a university statement, “this improved version of the protein could reduce the size of each dose or speed up vaccine production. Either way, it could mean more patients have access to vaccines faster.”

The university applied for patents on the synthetic protein technology, and already granted a non-exclusive license to Sino Biological, a chemical and biologics manufacturer. However, the HexaPro also carries a Creative Commons – Attribution license, and its plasmid can be acquired through AddGene.

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