ISCOM-Matrices Nanoformulation Using the Raw Aqueous Extract of Quillaja lancifolia (Q. brasiliensis)

Abstract

Quillaja saponins have an intrinsic capacity to interact with membrane lipids that self-assembles in nanoparticles (immunostimulating complexes or ISCOM-matrices) with outstanding immunoadjuvant activity and low toxicity profile. However, the expensive and laborious purification processes applied to purify Quillaja saponins used to assemble ISCOM-matrices show an important drawback in the large-scale use of this vaccine adjuvant. Thus, in this study, we describe a protocol to appropriately formulate ISCOM-matrices using the raw aqueous extract (AE) of Quillaja lancifolia leaves. In the presence of lipids, AE was able to self-assemble in nanostructures that resembles immunostimulating complexes (ISCOM). These negatively charged nanoparticles of approximately 40 nm were characterized by transmission electron microscopy and dynamic light scattering. In addition, well-known saponins with remarkable immunoadjuvant activity, as QS-21, were detected into nanoparticles. Thus, the easier, robust, cheaper, and environmentally friendly method developed here may be an alternative to the classical methods for ISCOM-matrices production that use high-purified saponins. Graphical abstract

Quillaja brasiliensis nanoparticle adjuvant formulation improves the efficacy of an inactivated trivalent influenza vaccine in mice

“…Novavax, Inc. has recently announced that the Matrix-M-adjuvanted quadrivalent nanoparticle influenza vaccine was immunologically comparable to the licensed quadrivalent inactivated influenza vaccine for older adults ( 34 ). In the last decade, we have reported experimental evidence of chemical similarities ( 12 , 21 ) and adjuvant activity of saponins belonging to the Quillajaceae family when they are co-formulated with a variety of viral antigens ( 9 , 12 , 20 , 22 , 23 , 26 , 31 ). The potential of QB saponins to offer alternative sources of QS-21 for use is clearly due to recent reports from our team ( 12 , 21 ) and others ( 24 , 48 ).…”

“…In the last decade, we have reported experimental evidence of chemical similarities ( 12 , 21 ) and adjuvant activity of saponins belonging to the Quillajaceae family when they are co-formulated with a variety of viral antigens ( 9 , 12 , 20 , 22 , 23 , 26 , 31 ). The potential of QB saponins to offer alternative sources of QS-21 for use is clearly due to recent reports from our team ( 12 , 21 ) and others ( 24 , 48 ).…”

“…Over the last decade, our research team has been studying saponins extracted from the leaves of Quillaja brasiliensis (QB) as an alternative to saponins extracted from Quillaja saponaria tree bark ( 9 , 20 – 23 ). Comprehensive chemical characterization has shown that the two species share a myriad of saponin structures, including well-known saponins with high immunoadjuvant activity, as well as QS-21 ( 12 , 21 , 24 ), a potent adjuvant isolated from the Q. saponaria tree and which is currently used in a few licensed vaccines ( 8 , 10 , 25 ). Furthermore, several studies have shown the immunoadjuvant potential of saponins from QB and their ability to form ISCOM-like nanostructures ( 9 , 11 , 21 , 22 , 26 ).…”

“…Comprehensive chemical characterization has shown that the two species share a myriad of saponin structures, including well-known saponins with high immunoadjuvant activity, as well as QS-21 ( 12 , 21 , 24 ), a potent adjuvant isolated from the Q. saponaria tree and which is currently used in a few licensed vaccines ( 8 , 10 , 25 ). Furthermore, several studies have shown the immunoadjuvant potential of saponins from QB and their ability to form ISCOM-like nanostructures ( 9 , 11 , 21 , 22 , 26 ). Thus, leaves of QB are a readily renewable source of these important secondary metabolites of high added value and of relevant importance for public health ( 9 , 26 ).…”