title: Needle-Free Dermal Delivery of a Diphtheria Toxin CRM197 Mutant on Potassium-Doped Hydroxyapatite Microparticles.
abstract: 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.
authors: Oxford Vaccine Group, Department of Pediatrics, University of Oxford, and NIHR Oxford Biomedical Research Institute, Oxford, United Kingdom Biomedical Ultrasonics, Biotherapy & Biopharmaceuticals Laboratory, University of Oxford, Oxford, United Kingdom The Oxford Martin School, University of Oxford, Old Indian Institute, Oxford, United Kingdom nikolas.weissmueller@gmail.com.
authors: Nikolas T
authors: NT
authors: Weissmueller
authors: Biomedical Ultrasonics, Biotherapy & Biopharmaceuticals Laboratory, University of Oxford, Oxford, United Kingdom.
authors: Heiko A
authors: HA
authors: Schiffter
authors: Biomedical Ultrasonics, Biotherapy & Biopharmaceuticals Laboratory, University of Oxford, Oxford, United Kingdom.
authors: Robert C
authors: RC
authors: Carlisle
authors: Oxford Vaccine Group, Department of Pediatrics, University of Oxford, and NIHR Oxford Biomedical Research Institute, Oxford, United Kingdom The Oxford Martin School, University of Oxford, Old Indian Institute, Oxford, United Kingdom.
authors: Christine S
authors: CS
authors: Rollier
authors: Oxford Vaccine Group, Department of Pediatrics, University of Oxford, and NIHR Oxford Biomedical Research Institute, Oxford, United Kingdom The Oxford Martin School, University of Oxford, Old Indian Institute, Oxford, United Kingdom.
authors: Andrew J
authors: AJ
authors: Pollard
mesh_terms: D000279:Administration, Cutaneous; D000327:Adsorption; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004167:Diphtheria Toxin / Q000276:immunology*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D011188:Potassium
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004167:Diphtheria Toxin; D004337:Drug Carriers; D007074:Immunoglobulin G; C028581:CRM197 (non-toxic variant of diphtheria toxin); D017886:Durapatite; D011188:Potassium