A solid approach to biopharmaceutical stabilisation

Aswin Doekhie; Rajeev Dattani; Yun-Chu Chen; Yi Yang; Andrew Smith; Alex P. Silve; Francoise Koumanov; Karen J. Edler; Kevin J. Marchbank; Jean van den Elsen; Asel Sartbaeva

doi:10.1038/s41598-020-65876-3

arXiv · 1811.12291

A solid approach to biopharmaceutical stabilisation

Aswin Doekhie·Rajeev Dattani·Yun-Chu Chen·Yi Yang·Andrew Smith·Alex P. Silve·Francoise Koumanov·Karen J. Edler·Kevin J. Marchbank·Jean van den Elsen·Asel Sartbaeva

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Abstract

Ensilication is a technology we developed that can physically stabilise proteins in silica without use of a pre-formed particle matrix. Stabilisation is done by tailor fitting individual proteins with a silica coat using a modified sol-gel process. Biopharmaceuticals, for example, liquid-formulated vaccines with adjuvants, have poor thermal stability. Heating or freezing impairs their potency. As a result, there is an increase in the prevalence of vaccine-preventable diseases in low-income countries even when there are means to combat them. One of the root causes lies in the problematic vaccine cold-chain distribution. We believe that ensilication can improve vaccine availability by enabling transportation without refrigeration. Here, we show that ensilication stabilises tetanus toxoid C fragment (TTCF) and demonstrate that this material can be stored and transported at ambient temperature without compromising the immunogenic properties of TTCF in vivo. TTCF is a component of the diphtheria, tetanus and pertussis (DTP) vaccine. To further our understanding of the ensilication process, and its protective effect on proteins we have studied the formation of TTCF-silica nanoparticles via time-resolved Small Angle X-ray Scattering (SAXS). Our results reveal ensilication to be a staged diffusion-limited cluster aggregation (DLCA) type reaction, induced by the presence of TTCF protein at neutral pH. Analysis of scattering data indicates tailor fitting of TTCF protein. The experimental in vivo immunisation data confirms the retention of immunogenicity after release from silica. Our results suggest that we could utilise this technology for multicomponent vaccines, therapeutics or other biopharmaceuticals that are not compatible with lyophilisation.

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Aswin Doekhie, Rajeev Dattani, Yun-Chu Chen, Yi Yang, Andrew Smith, Alex P. Silve, Francoise Koumanov, Karen J. Edler, Kevin J. Marchbank, Jean van den Elsen, Asel Sartbaeva. 2018-11-29. A solid approach to biopharmaceutical stabilisation. https://doi.org/10.1038/s41598-020-65876-3

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