期刊
BIOLOGICALS
卷 75, 期 -, 页码 21-28出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biologicals.2021.12.001
关键词
Rotavirus vaccine; RV3-BB; Formulation; Stability; Linear regression; Arrhenius equation
资金
- Bill and Melinda Gates Foundation [OPP1148427, OPP1111055, OPP 11183101]
- Australian National Health and Medical Research Council [APP491238, APP1012425, APP546496]
- Victorian Government Infrastructure Grant
- Bill and Melinda Gates Foundation [OPP1111055, OPP1148427] Funding Source: Bill and Melinda Gates Foundation
This study used linear regression and Arrhenius modeling to predict the real-time stability profiles of a live-virus vaccine. The predictions were validated using high-throughput assays and control groups, and the study concluded with a ranking of the vaccine formulations.
To accelerate the formulation development of live-virus vaccine (LW) candidates, more rapid approaches to rank-order formulations and estimate their real-time storage stability losses are needed. In this case-study, we utilize new and previously described stability data of a live, rotavirus vaccine candidate (RV3-BB) in three different liquid formulations to model and compare predicted vs. experimental RV3-BB stability profiles. Linear-regression extrapolations of limited real-time (2-8 degrees C) stability data and Arrhenius modeling of accelerated (15, 25, 37 degrees C) stability data provided predictions of RV3-BB real-time stability profiles (2-8 degrees C, 24 months). Good correlations of modeled versus experimental stability data to rank-order the RV3-BB formulations were achieved by employing (1) a high-throughput RT-qPCR assay to measure viral titers, (2) additional assay replicates and stability time-points, and (3) a -80 degrees C control for each formulation to benchmark results at each stability time-point and temperature. Instead of accumulating two-year, 2-8 degrees C storage stability data, the same rank-ordering of the three RV3-BB formulations could have been achieved by modeling 3T, 25 degrees, 15 degrees (and 2-8 degrees C) stability data over 1, 3 and 12 months, respectively. The results of this case-study are discussed in the context of accelerating LW formulation development by expeditiously identifying stable formulations, estimating their shelf-lives, and determining vaccine vial monitoring (VVM) designations.
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