Formulation Development and Improved Stability of a Combination Measles and Rubella Live-Viral Vaccine Dried for Use in the Nanopatch(TM) Microneedle Delivery System
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Issue Date
2021-05-06Author
Wan, Ying
Gupta, Vineet
Bird, Christopher
Pullagurla, Swathi R.
Fahey, Paul
Forster, Angus
Volkin, David B.
Joshi, Sangeeta B.
Publisher
Taylor and Francis
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. This work is licensed under a Creative Commons Attribution 4.0 International License.
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Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low – and middle – income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch™, a solid polymer micro-projection array for intradermal delivery. First, high throughput, qPCR-based viral infectivity and genome assays were established to enable formulation development to stabilize Me and Ru in a scaled-down, custom-built evaporative drying system to mimic the Nanopatch™ vaccine coating process. Second, excipient screening and optimization studies identified virus stabilizers for use during the drying process and upon storage in the dried state. Finally, a series of real-time and accelerated stability studies identified eight candidate formulations that met a target thermal stability criterion for live vaccines (<1 log10 loss after 1 week storage at 37°C). Compared to −80°C control samples, the top candidate formulations resulted in minimal viral infectivity titer losses after storage at 2–8°C for 6 months (i.e., <0.1 log10 for Me, and ~0.4 log10 for Ru). After storage at 25°C over 6 months, ~0.3–0.5 and ~1.0–1.4 log10 titer losses were observed for Me and Ru, respectively, enabling the rank-ordering of the stability of candidate formulations. These results are discussed in the context of future formulation challenges for developing microneedle-based dosage forms containing stabilized live, attenuated viral vaccines for use in LMICs.
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Citation
Wan, Y., Gupta, V., Bird, C., Pullagurla, S. R., Fahey, P., Forster, A., Volkin, D. B., & Joshi, S. B. (2021). Formulation Development and Improved Stability of a Combination Measles and Rubella Live-Viral Vaccine Dried for Use in the NanopatchTM Microneedle Delivery System. Human vaccines & immunotherapeutics, 17(8), 2501–2516. https://doi.org/10.1080/21645515.2021.1887692
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