1. Kilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.
- Author
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Fisher KJ, Shirtcliff L, Buchanan G, Thompson AW, Woolard FX, LaMunyon DH, Marshall JL, Baranouskas MB, Voelker RB, Lusk JS, Wells CE, Mohamath R, Kinsey R, Lykins WR, Ramer-Denisoff G, Fox CB, Paddon CJ, and McPhee D
- Abstract
Emulsions of the triterpene squalene ((6 E ,10 E ,14 E ,18 E )-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of trans -β-farnesene ((6 E )-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process. The scalability of the proposed route was verified by a kilo-scale GMP synthesis. We also report data demonstrating the synthesized semi-synthetic squalene's physical stability and biological activity when used in a vaccine adjuvant formulation., Competing Interests: Competing Interests All authors declare no competing non-financial interests, but the following declare competing financial interests: C.J.P., G.B., A.W.T. and D.J.M. own shares and possess stock options in Amyris, Inc. F.X.W. owns shares in Amyris, Inc. C.B.F. is an inventor on patents and/or patent applications involving terpenoid emulsion adjuvant formulations. K.J.F. and F.X.W. are inventors on a patent application involving the synthesis of squalene from farnesene.
- Published
- 2023
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