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Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization
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 w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280242/ https://www.ncbi.nlm.nih.gov/pubmed/32513957 http://dx.doi.org/10.1038/s41598-020-65876-3 |
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author | Doekhie, A. Dattani, R. Chen, Y-C. Yang, Y. Smith, A. Silve, A. P. Koumanov, F. Wells, S. A. Edler, K. J. Marchbank, K. J. Elsen, J. M. H. van den Sartbaeva, A. |
author_facet | Doekhie, A. Dattani, R. Chen, Y-C. Yang, Y. Smith, A. Silve, A. P. Koumanov, F. Wells, S. A. Edler, K. J. Marchbank, K. J. Elsen, J. M. H. van den Sartbaeva, A. |
author_sort | Doekhie, A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7280242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72802422020-06-15 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. Marchbank, K. J. Elsen, J. M. H. van den Sartbaeva, A. Sci Rep Article 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. Nature Publishing Group UK 2020-06-08 /pmc/articles/PMC7280242/ /pubmed/32513957 http://dx.doi.org/10.1038/s41598-020-65876-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Doekhie, A. Dattani, R. Chen, Y-C. Yang, Y. Smith, A. Silve, A. P. Koumanov, F. Wells, S. A. Edler, K. J. Marchbank, K. J. Elsen, J. M. H. van den Sartbaeva, A. Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title | Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title_full | Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title_fullStr | Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title_full_unstemmed | Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title_short | Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization |
title_sort | ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved saxs characterization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280242/ https://www.ncbi.nlm.nih.gov/pubmed/32513957 http://dx.doi.org/10.1038/s41598-020-65876-3 |
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