February 23, 2023 report

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Synthesizing squalene to reduce need for shark liver oil

by Bob Yirka , Medical Xpress

Synthesizing squalene to reduce need for shark liver oil
Effects of terpenoid oil emulsions on antigen-specific HAI, total IgG, and long-lived antibody-secreting plasma cells in mice immunized intramuscularly with split, inactivated H5N1 influenza antigen mixed with terpenoid emulsions. Vaccine antigen was mixed with the indicated terpenoid oil emulsion immediately prior to intramuscular immunization of C57BL/6 mice (male [open circles] and female [closed circles]) such that each animal received 10 ng of antigen in 100 µL of 2% v/v terpenoid emulsion. Negative control groups received antigen alone (None) or antigen mixed with long-chain triglyceride emulsion. Three separate experiments each with different terpenoids as indicated are represented (a–c, d–f, and g–i). Data are represented as box-whisker plots with bars representing median values, boxes representing 1st–3rd quartiles, and whiskers representing the maximum and minimum values. Statistical evaluation of each terpenoid emulsion group compared to antigen alone (negative control) and shark squalene emulsion (positive control) was performed by one-way ANOVA with Sidak’s correction for multiple comparisons or Kruskal–Wallis test with Dunn’s correction for multiple comparisons as indicated; *p-value < 0.05, **p-value < 0.01, ***p-value < 0.001, ****p-value < 0.0001. a, d, g Antigen-specific total IgG (IgGT) serum titers measured by ELISA 42 days after prime immunization (n = 7–8 mice, one-way ANOVA). b, e, h Long-lived antibody-secreting cells in the bone marrow measured by ELISpot assay 42 days after prime immunization (n = 8 mice, Kruskal–Wallis for b; n = 4–8 mice, one-way ANOVA for e; n = 8 mice, one-way ANOVA for h). c, f, i HAI titers measured 42 days after prime immunization (n = 8 mice, one-way ANOVA for c; n = 7–8 mice, Kruskal–Wallis for f, i). Credit: npj Vaccines (2023). DOI: 10.1038/s41541-023-00608-y

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 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 . 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 .

During testing, the team found that a few of the analogs actually performed better than native 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 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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Citation: Synthesizing squalene to reduce need for shark liver oil (2023, February 23) retrieved 22 June 2024 from https://medicalxpress.com/news/2023-02-squalene-shark-liver-oil.html
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