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

Doekhie, A. ; Dattani, R. ; Chen, Y-C. ; Yang, Y. ; Smith, A. ; Silve, A. P. ; Koumanov, F. ; Wells, S. A. ; Edler, K. J. LU orcid and Marchbank, K. J. , et al. (2020) In Scientific Reports 10(1).
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 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.... (More)

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 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 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.

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publishing date
type
Contribution to journal
publication status
published
in
Scientific Reports
volume
10
issue
1
article number
9243
publisher
Nature Publishing Group
external identifiers
  • pmid:32513957
  • scopus:85086173090
ISSN
2045-2322
DOI
10.1038/s41598-020-65876-3
language
English
LU publication?
no
additional info
Publisher Copyright: © 2020, The Author(s).
id
01b7a272-39e7-4e9c-9fe3-961828e19c15
date added to LUP
2023-01-18 08:59:45
date last changed
2024-04-18 10:03:44
@article{01b7a272-39e7-4e9c-9fe3-961828e19c15,
  abstract     = {{<p>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 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 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.</p>}},
  author       = {{Doekhie, A. and Dattani, R. and Chen, Y-C. and Yang, Y. and Smith, A. and Silve, A. P. and Koumanov, F. and Wells, S. A. and Edler, K. J. and Marchbank, K. J. and van den Elsen, J. M. H. and Sartbaeva, A.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Ensilicated tetanus antigen retains immunogenicity : <i>in vivo</i> study and time-resolved SAXS characterization}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-65876-3}},
  doi          = {{10.1038/s41598-020-65876-3}},
  volume       = {{10}},
  year         = {{2020}},
}