Synthesizing squalene to reduce need for shark liver oil

A team of medical researchers from Amyris, Inc. and the Access to Advanced Health Institute has developed a new way to synthesize squalene, a natural terpene used to boost the effectiveness of several vaccines. In their paper published in npj Vaccines, the group describes their new approach and how well it worked.

Squalene has been used with many vaccines since the 1990s, when it was found to boost their effectiveness—some of the most well known are vaccines for the flu, COVID-19, tuberculosis and malaria. Unfortunately, the main source of squalene is shark liver oil, which means that sharks must be caught and killed to obtain the substance.

Noting that shark populations have been dropping dramatically in recent years, scientists have been looking for new sources of the organic compound. Squalene is produced by nearly all plants and animals, but not in ways that are viable, except for sharks. So research has switched to finding ways to produce the material in the lab.

In this new effort, the team used ß-farnesene, a compound created during the fermentation of yeast. Synthesis was carried out using the compound to create 20 versions of squalene, each of which was tested to see how well it performed in boosting the effectiveness of several vaccines.

The researchers added the analogs individually to blood assays and measured the immune response. Notably, ß-farnesene is already produced by Amyris, Inc., which has members on the research team—it is used in drugs that help to reduce inflammation and to fight bacterial and fungal infections.

During testing, the team found that a few of the analogs actually performed better than native squalene produced by sharks. But a lot of them did worse. The team found that in high-performing analogs, chains of isoprene units that were longer tended to perform better. They also found that chain saturation was a factor.

The research team plans to continue their work, but expect that one or more of their synthetically produced squalenes will be ready for clinical trials soon.

More information:
Karl J. Fisher et al, Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions, npj Vaccines (2023). DOI: 10.1038/s41541-023-00608-y

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