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Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization

Lookup NU author(s): Professor Kevin Marchbank

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Our recently developed ensilication approach can physically stabilize 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, e.g. liquid-formulated vaccines with adjuvants, frequently have poor thermal stability; heating and/or freezing impairs their potency. As a result, there is an increase in the prevalence of vaccine-preventable diseases in lowincome 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 stabilizes tetanus toxin C fragment (TTCF), a component of the tetanus toxoid present in the diphtheria, tetanus and pertussis (DTP) vaccine. Experimental in vivo immunization data show that the ensilicated material can be stored, transported at ambient temperatures, and even heat-treated without compromising the immunogenic properties of TTCF. To further our understanding of the ensilication process and its protective effect on proteins, we have also 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. An early stage (tens of seconds) in which individual proteins are coated with silica is followed by a subsequent stage (several minutes) in which the protein-containing silica nanoparticles aggregate into larger clusters. Our results suggest that we could utilize this technology for vaccines, therapeutics or other biopharmaceuticals that are not compatible with lyophilization.


Publication metadata

Author(s): Doekhie A, Dattani R, Chen Y-C, Yang Y, Smith A, Silve AP, Koumanov F, Wells SA, Edler KJ, Marchbank KJ, van-den-Elsen JMH, Sartbaeva A

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2020

Volume: 10

Online publication date: 08/06/2020

Acceptance date: 20/02/2020

Date deposited: 25/06/2020

ISSN (electronic): 2045-2322

Publisher: Nature

URL: https://doi.org/10.1038/s41598-020-65876-3

DOI: 10.1038/s41598-020-65876-3


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