Virus-like particle formulation optimization by miniaturized high-throughput screening

Mohr, Johannes, Chuan, Yap P., Wu, Yang, Lua, Linda H. L. and Middelberg, Anton P. J. (2013) Virus-like particle formulation optimization by miniaturized high-throughput screening. Methods, 60 3: 248-256. doi:10.1016/j.ymeth.2013.04.019

Author Mohr, Johannes
Chuan, Yap P.
Wu, Yang
Lua, Linda H. L.
Middelberg, Anton P. J.
Title Virus-like particle formulation optimization by miniaturized high-throughput screening
Journal name Methods   Check publisher's open access policy
ISSN 1046-2023
Publication date 2013-05
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ymeth.2013.04.019
Volume 60
Issue 3
Start page 248
End page 256
Total pages 9
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Collection year 2014
Language eng
Formatted abstract
Virus-like particles (VLPs) are non-infectious and immunogenic virus-mimicking protein assemblies that are increasingly researched as vaccine candidates. Stability against aggregation is an important determinant dictating the viability of a pipeline VLP product, making multivariable stability data highly desirable especially in early product development stages. However, comprehensive formulation studies are challenging due to low sample availability early in developability assessment. This issue is exacerbated by industry-standard analytical techniques which are low-throughput and/or sample-consuming. This study presents a miniaturized high-throughput screening (MHTS) methodology for VLP formulation by integrating dynamic light scattering (DLS) and asymmetrical flow field-flow fractionation (AF4) in a formulation funnel analysis. Using only 2. μg of sample and 100. s per measurement, a DLS plate reader was deployed to effectively pre-screen a large experimental space, allowing a smaller set of superior formulation conditions to be interrogated at high-resolution with AF4. The stabilizing effects of polysorbate 20, sucrose, trehalose, mannitol and sorbitol were investigated. MHTS data showed that addition of 0.5% w/v polysorbate 20 together with either 40% w/v sucrose or 40% w/v sorbitol could stabilize VLPs at elevated temperatures up to 58. °C. AF4 data further confirmed that the formulation containing 40% w/v sorbitol and 0.5% w/v polysorbate 20 effectively protected VLPs during freeze-thawing and freeze-drying, increasing recoveries from these processes by 80 and 50 percentage points, respectively. The MHTS strategy presented here could be used to rapidly explore a large formulation development space using reduced amounts of sample, without sacrificing the analytical resolution needed for quality control. Such a method paves the way for rapid formulation development and could potentially hasten the commercialization of new VLP vaccines.
Keyword Miniaturization
High throughput
Virus like particles
Freeze thaw
Freeze drying
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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