Kilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.
Org Process Res Dev
; 27(12): 2317-2328, 2023 Dec 15.
Article
in En
| MEDLINE
| ID: mdl-38524776
ABSTRACT
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 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-ß-farnesene ((6E)-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Org Process Res Dev
Year:
2023
Document type:
Article
Affiliation country:
United States