Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 06 2020
08 06 2020
Historique:
received:
13
11
2019
accepted:
30
03
2020
entrez:
10
6
2020
pubmed:
10
6
2020
medline:
15
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32513957
doi: 10.1038/s41598-020-65876-3
pii: 10.1038/s41598-020-65876-3
pmc: PMC7280242
doi:
Substances chimiques
Tetanus Toxoid
0
Silicon Dioxide
7631-86-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9243Subventions
Organisme : Medical Research Council
ID : MC_PC_15030
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P002927/1
Pays : United Kingdom
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