Synthesis and Evaluation of QS-7-Based Vaccine Adjuvants (CROSBI ID 715259)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Škalamera, Đani ; Wang, Pengfei ; Sui, Xianwei ; Zhang, Ping ; Michalek, Suzanne M.
engleski
Synthesis and Evaluation of QS-7-Based Vaccine Adjuvants
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 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 designed and synthesized two analogs (3 and 4) of QS-7, a natural saponin isolated from Quillaja saponaria Molina tree bark. The only structural difference between compounds 3 and 4 is that 3 is acetylated at the 3- and 4-O positions of the quillaic acid C28 fucosyl unit, whereas 4 is not. Interestingly, the immunostimulant profiles of the two compounds are significantly different. Compound 3 potentiates a mixed Th1/Th2 (Th, T helper cells) immune response against the tested antigens, whereas compound 4 showed induction of Th2-biased immunity only. These results suggest that the 3- and 4-O acetyl groups of the fucosyl unit may play an important role in tuning the adjuvanticity of the QS-7 analogs. Compound 3 can serve as a structurally defined synthetic adjuvant when a mixed Th1/Th2 immune response is desired and also as a molecular probe for mechanistic studies.
Quillaja saponaria, immunoadjuvants, oligosaccharide synthesis
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Podaci o prilogu
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2020.
objavljeno
Podaci o matičnoj publikaciji
7th EFMC Young Medicinal Chemists’ Symposium
Podaci o skupu
7th EFMC Young Medicinal Chemists’ Symposium
pozvano predavanje
10.09.2020-11.09.2020
online