Naslov
Synthesis and Evaluation of QS-17/18-Based Vaccine Adjuvant

Autori
Škalamera, Đani

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
3rd Mini-Symposium of Medicinal and Pharmaceutical Chemistry

Mjesto i datum
Zagreb, Hrvatska, 12.11.2019

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
immunoadjuvants ; Quillaja saponaria ; organic synthesis ; carbohydrate chemistry ; natural product synthesis

Sažetak
There is increasing interest in developing new vaccines against cancers, infectious diseases and degenerative disorders. Vaccine adjuvant is a substance formulated as part of a vaccine boost and/or modulates the antigen-specific immune responses. Recently, QS-21 was approved as a component of the GlaxoSmithKline’s AS01b adjuvant formulation for the human vaccine Shingrix. QS-21 is a mixture of two isomeric saponins extracted from the bark of Quillaja saponaria (QS) Molina. It has been studied in over one hundred clinical trials of vaccines against cancers and infectious diseases. However, it has its own drawbacks including chemical instability, dose-limiting toxicity, limited supply, and laborious and low-yielding purification. Significant efforts have been devoted to developing synthetic analogs of QS- 21 to overcome the limitations of the natural product. We have synthesized a QS-17/18 analogue 4 and evaluated its adjuvant activity in the formulation with rHagB antigen. Compound 4 and deacetylated QS-21 analogues (compounds 1 with R5 = H) are the major components of GPI-0100, a widely used complex mixture of semisynthetic derivatives of QS saponins. The QS-17/18 analogue 4 shows an adjuvant activity profile similar to that of GPI-0100, potentiating mixed Th-1/Th-2 immune responses, which is different from those of deacetylated QS-21 analogues that induce only a Th2-like immunity. The combination of QS-17/18 and QS-21 analogues does not show a synergistic effect. These results suggest that QS-17/18 analogue 4 might be the active component of GPI-0100 responsible for its immunostimulant property. Therefore, compound 4 can not only be a structurally defined alternative to GPI-0100, but also provide a valuable clue for rational design of new QS-based vaccine adjuvants with better adjuvant properties.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA