Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles
Injections with a hypodermic needle and syringe (HNS) are the current standard of care globally, but the use of needles is not without limitation. While a plethora of needle-free injection devices exist, vaccine reformulation is costly and presents a barrier to their widespread clinical application....
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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American Society for Microbiology
2015
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| _version_ | 1826303782331351040 |
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| author | Weissmueller, N Schiffter, H Carlisle, R Rollier, C Pollard, A |
| author_facet | Weissmueller, N Schiffter, H Carlisle, R Rollier, C Pollard, A |
| author_sort | Weissmueller, N |
| collection | OXFORD |
| description | Injections with a hypodermic needle and syringe (HNS) are the current standard of care globally, but the use of needles is not without limitation. While a plethora of needle-free injection devices exist, vaccine reformulation is costly and presents a barrier to their widespread clinical application. To provide a simple, needle-free, and broad-spectrum protein antigen delivery platform, we developed novel potassium-doped hydroxyapatite (K-Hap) microparticles with improved protein loading capabilities that can provide sustained local antigen presentation and release. K-Hap showed increased protein adsorption over regular hydroxyapatite (P < 0.001), good structural retention of the model antigen (CRM197) with 1% decrease in α-helix content and no change in β-sheet content upon adsorption, and sustained release in vitro. Needle-free intradermal powder inoculation with K-Hap-CRM197 induced significantly higher IgG1 geometric mean titers (GMTs) than IgG2a GMTs in a BALB/c mouse model (P < 0.001) and induced IgG titer levels that were not different from the current clinical standard (P > 0.05), namely, alum-adsorbed CRM197 by intramuscular (i.m.) delivery. The presented results suggest that K-Hap microparticles may be used as a novel needle-free delivery vehicle for some protein antigens. |
| first_indexed | 2024-03-07T06:07:55Z |
| format | Journal article |
| id | oxford-uuid:ee7aa39e-7457-4217-ae1d-7d1ee7a6971e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:07:55Z |
| publishDate | 2015 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:ee7aa39e-7457-4217-ae1d-7d1ee7a6971e2022-03-27T11:33:03ZNeedle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticlesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ee7aa39e-7457-4217-ae1d-7d1ee7a6971eEnglishSymplectic Elements at OxfordAmerican Society for Microbiology2015Weissmueller, NSchiffter, HCarlisle, RRollier, CPollard, AInjections with a hypodermic needle and syringe (HNS) are the current standard of care globally, but the use of needles is not without limitation. While a plethora of needle-free injection devices exist, vaccine reformulation is costly and presents a barrier to their widespread clinical application. To provide a simple, needle-free, and broad-spectrum protein antigen delivery platform, we developed novel potassium-doped hydroxyapatite (K-Hap) microparticles with improved protein loading capabilities that can provide sustained local antigen presentation and release. K-Hap showed increased protein adsorption over regular hydroxyapatite (P < 0.001), good structural retention of the model antigen (CRM197) with 1% decrease in α-helix content and no change in β-sheet content upon adsorption, and sustained release in vitro. Needle-free intradermal powder inoculation with K-Hap-CRM197 induced significantly higher IgG1 geometric mean titers (GMTs) than IgG2a GMTs in a BALB/c mouse model (P < 0.001) and induced IgG titer levels that were not different from the current clinical standard (P > 0.05), namely, alum-adsorbed CRM197 by intramuscular (i.m.) delivery. The presented results suggest that K-Hap microparticles may be used as a novel needle-free delivery vehicle for some protein antigens. |
| spellingShingle | Weissmueller, N Schiffter, H Carlisle, R Rollier, C Pollard, A Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title | Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title_full | Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title_fullStr | Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title_full_unstemmed | Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title_short | Needle-free dermal delivery of a diphtheria toxin CRM197 mutant on potassium-doped hydroxyapatite microparticles |
| title_sort | needle free dermal delivery of a diphtheria toxin crm197 mutant on potassium doped hydroxyapatite microparticles |
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