Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation.

Dulal P., Gharaei R., Berg A., Walters AA., Hawkins N., Claridge TDW., Kowal K., Neill S., Ritchie AJ., Ashfield R., Hill AVS., Tronci G., Russell SJ., Douglas AD.

Adenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2-8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.

DOI

10.1038/s41598-021-00065-4

Type

Journal article

Journal

Scientific reports

Publication Date

22/10/2021

Volume

11

Addresses

Jenner Institute, University of Oxford, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK. pawan.dulal@enesipharma.com.

Keywords

Humans, Adenoviridae, Adenoviruses, Simian, Polyvinyl Alcohol, Glass, Trehalose, Rabies Vaccines, Biocompatible Materials, Microscopy, Confocal, Microscopy, Electron, Scanning, Calorimetry, Differential Scanning, Spectroscopy, Fourier Transform Infrared, Magnetic Resonance Spectroscopy, Thermogravimetry, Materials Testing, Temperature, Light, Scattering, Radiation, HEK293 Cells, Vaccine Potency, Adenovirus Vaccines, Sugars, COVID-19, COVID-19 Vaccines

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