Synthetic saponin derivatives act as functional subunit vaccine adjuvants through an NLRP3-inflammasome-independent mechanism

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B964
Abstract ID: 7664

Presenting Author:
Austin Santhin , Graduate Student at St. Jude Grad. Sch. of Biomed. Sci.

Abstract:

Quillaja saponaria 21 (QS-21) is a saponin compound extracted from the bark of a South American evergreen tree. The ability of QS-21 to induce robust cellular and humoral immunity as an adjuvant led to it being evaluated in multiple clinical vaccine trials. However, mechanistic and toxicity questions following its purification hinder its potential use and led to the search for suitable alternative adjuvants. A group of 14 novel synthetic compounds have been chemically derived from a less toxic saponin, lablaboside F, to be tested as suitable alternatives to QS-21. When administered with an OVA peptide antigen intramuscularly into C57BL/6 mice using a prime-boost strategy, compound JG-151 elicited increased production of OVA-specific total IgG antibodies 2 weeks post-boost compared to control mice. When analyzed in vitro, JG-151 displayed decreased cellular toxicity 24 hrs post-treatment compared to QS-21. However, JG-151 neither activated NF-kB alone nor induced significant production of the pro-inflammatory cytokine IL-1ß with MPLA 24 hrs post-treatment. These results indicate JG-151 does not activate the NLRP3 inflammasome, in contrast to QS-21. Our results demonstrate that novel saponin derivatives, such as JG-151, safely elicit humoral immunity through an NLRP3 inflammasome-independent mechanism and could serve as suitable subunit vaccine adjuvant alternatives to QS-21.