title: Repeated fractional intradermal dosing of an inactivated polio vaccine by a single hollow microneedle leads to superior immune responses.
abstract: The purpose of this study was to investigate the effect of various repeated fractional intradermal dosing schedules of inactivated polio vaccine serotype 1 (IPV1) on IPV1-specific IgG responses in rats. By utilizing an applicator that allowed for precisely controlled intradermal microinjections by using a single hollow microneedle, rats were immunized intradermally with 5 D-antigen units (DU) of IPV1 at 150μm skin depth. This dose was administered as a bolus, or in a repeated fractional dosing schedule: 4 doses of 1.25 DU (1/4th of total dose) were administered on four consecutive days or every other day; 8 doses of 0.625 DU (1/8th of total dose) were administered on eight consecutive days; or 4 exponentially increasing doses (0.04, 0.16, 0.8 and 4 DU), either with or without an exponentially increasing CpG oligodeoxynucleotide 1826 (CpG) dose, were administered on four consecutive days. All of these fractional dosing schedules resulted in up to ca. 10-fold higher IPV1-specific IgG responses than intradermal and intramuscular bolus dosing. IPV1 combined with adjuvant CpG in exponential dosing did not significantly increase the IPV1-specific IgG responses further, which demonstrated that maximal responses were achieved by fractional dosing. In conclusion, repeated fractional intradermal IPV1 dosing leads to superior IPV1-specific IgG responses without the use of adjuvants. These results indicate that a controlled release delivery system for intradermal IPV1 delivery can potentiate IPV1-specific IgG responses.
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: p.schipper@lacdr.leidenuniv.nl.
authors: Pim
authors: P
authors: Schipper
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: k.van.der.maaden@lacdr.leidenuniv.nl.
authors: Koen
authors: K
authors: van der Maaden
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: romeijn@lacdr.leidenuniv.nl.
authors: Stefan
authors: S
authors: Romeijn
authors: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. Electronic address: c.w.j.oomens@tue.nl.
authors: Cees
authors: C
authors: Oomens
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands. Electronic address: gideon.kersten@intravacc.nl.
authors: Gideon
authors: G
authors: Kersten
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: w.jiskoot@lacdr.leidenuniv.nl.
authors: Wim
authors: W
authors: Jiskoot
authors: Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: bouwstra@lacdr.leidenuniv.nl.
authors: Joke
authors: J
authors: Bouwstra
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D007271:Injections, Intradermal; D008845:Microinjections; D009339:Needles; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D003692:Delayed-Action Preparations; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011054:Poliovirus Vaccine, Inactivated
keywords: Adjuvant; Dose-sparing; Fractional dose; Hollow microneedles; Inactivated polio vaccine; Intradermal immunization; Poliomyelitis