Abstract
Quil-A and cholesterol can, under certain conditions, form nanoparticles, but the conditions for the formation of a homogeneous population of a particular kind of particles with the same morphology and size have remained elusive. However, a well-defined uniformity, as well as a high degree of batch-to-batch consistency, are prerequisites for adjuvant formulations to be used for practical vaccines. To accomplish the above stated tasks in the present study, we demonstrated that Quil-A and cholesterol form well-defined worm-like stable particles with a mean diameter of around 40 nm by dynamic light scattering (DLS) under carefully controlled thermodynamical conditions with little or no Quil-A degradation. The nanoparticles thus prepared possessed a significantly reduced hemolytic effect in comparison to unformulated free Quil-A. However, when the same conditions were applied to QS-21/cholesterol nanoparticle formation the morphology achieved was coil spring-like particles with a mean diameter of around 70 nm. This discrepancy in particle morphology and size was attributed to the differences in hydrophobicity of the Quil-A, being a heterogenic fraction of acylated as well as deacylated saponins, and the QS-21. With the process optimizations leading to a standardized particle size distribution and nanoparticle morphology presented here, NanoQuil F70 holds the potential as a well-tolerated vaccine adjuvant for veterinary use raising a Th1/Th2 balanced immune response.
Highlights
The triterpene saponin mixture Quil-A has been used as vaccine adjuvant in animals for many years, but its lytic and surfactant activity introduce limitations for the dose to be applied in order to balance the adjuvant effect against the local adverse reactions at the injection site [1] [2] [3]
To accomplish the above stated tasks in the present study, we demonstrated that Quil-A and cholesterol form well-defined worm-like stable particles with a mean diameter of around 40 nm by dynamic light scattering (DLS) under carefully controlled thermodynamical conditions with little or no Quil-A degradation
With the process optimizations leading to a standardized particle size distribution and nanoparticle morphology presented here, NanoQuil F70 holds the potential as a well-tolerated vaccine adjuvant for veterinary use raising a Th1/Th2 balanced immune response
Summary
The triterpene saponin mixture Quil-A has been used as vaccine adjuvant in animals for many years, but its lytic and surfactant activity introduce limitations for the dose to be applied in order to balance the adjuvant effect against the local adverse reactions at the injection site [1] [2] [3] This problem was at least partially overcome by Morein et al in 1984 by incorporating the Quil-A saponin into cage-like ISCOM particles when combined with cholesterol and phospholipids (PC) [4] and later with the ISCOMATRIX formulation [5]. The ability of triterpene saponins to interact with cholesterol alone was used by Morein, Hu et al to design a novel Quil-A containing nanoparticle, originally referred to as G3 and later re-named NanoQuil This formulation of Quil-A + cholesterol, when used as a vaccine adjuvant, generated an immune response overall similar to that of the traditional ISCOM formulation with a balanced Th-1/Th-2 profile. This new adjuvant formulation when supplemented with the diterpene, Stevia glycoside, known as a commonly used and GRAS food additive (sweetener) [6], could even induce cross-protective immunity again a range of influenza virus strains and stimulated a vast array of innate immune response parameters in vitro.
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