posted on 2023-11-16, 18:00authored byKarl J. Fisher, Laura Shirtcliff, Greg Buchanan, Andrew W. Thompson, Frank X. Woolard, Donald H. LaMunyon, Jonathan L. Marshall, Maya B. Baranouskas, Rodger B. Voelker, Jason S. Lusk, Charles E. Wells, Raodoh Mohamath, Robert Kinsey, William R. Lykins, Gabi Ramer-Denisoff, Christopher B. Fox, Christopher J. Paddon, Derek McPhee
Emulsions of the triterpene squalene ((6E,10E,14E,18E)-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
raise sustainability issues for a 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 ((6E)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene,
CAS 18794-84-8), manufactured from sustainable sugar cane 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 semisynthetic squalene’s physical stability and
biological activity when used in a vaccine adjuvant formulation.