Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Mizuki Tateno, Barbara J. Stone, Sarah J. Srodulski, Stephanie Reedy, Thomas R. Gawriluk, Thomas M. Chambers, Jerold Woodward, Joe Chappell, Chase F. Kempinski

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The triterpene oil squalene is an essential component of nanoemulsion vaccine adjuvants. It is most notably in the MF59 adjuvant, a component in some seasonal influenza vaccines, in stockpiled, emulsion-based adjuvanted pandemic influenza vaccines, and with demonstrated efficacy for vaccines to other pandemic viruses, such as SARS-CoV-2. Squalene has historically been harvested from shark liver oil, which is undesirable for a variety of reasons. In this study, we have demonstrated the use of a Synthetic Biology (yeast) production platform to generate squalene and novel triterpene oils, all of which are equally as efficacious as vaccine adjuvants based on physiochemical properties and immunomodulating activities in a mouse model. These Synthetic Biology adjuvants also elicited similar IgG1, IgG2a, and total IgG levels compared to marine and commercial controls when formulated with common quadrivalent influenza antigens. Injection site morphology and serum cytokine levels did not suggest any reactogenic effects of the yeast-derived squalene or novel triterpenes, suggesting their safety in adjuvant formulations. These results support the advantages of yeast produced triterpene oils to include completely controlled growth conditions, just-in-time and scalable production, and the capacity to produce novel triterpenes beyond squalene.

Original languageEnglish
Article number17090
JournalScientific Reports
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

Bibliographical note

Funding Information:
This research was sponsored by an NIH STTR (1R41AI141060-01) and Kentucky Cabinet for Economic Development STTR Matching Grant (CED-2018-001-08) to Enepret Incorporated, in which both Drs. Chappell and Kempinski have a financial interest. Dr. Gawriluk is employed at Enepret Incorporated. No other authors have competing interests to declare.

Funding Information:
We are thankful to Dr. Xun Zhuang for generation of the initial yeast platform and purification of some of the yeast-derived triterpenes used in this study. TMC and SR were supported in part by a project of the Kentucky Agricultural Experiment Station (KY014053).

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus subject areas

  • General

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