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: Pim Schipper, Koen van der Maaden, Stefan Romeijn, Cees Oomens, Gideon Kersten, Wim Jiskoot, Joke Bouwstra
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 242 Pg. 141-147 (11 28 2016) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 27496634 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• CPG-oligonucleotide
• Delayed-Action Preparations
• Immunoglobulin G
• Oligodeoxyribonucleotides
• Poliovirus Vaccine, Inactivated

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Delayed-Action Preparations
• Drug Administration Schedule
• Drug Delivery Systems
• Female
• Immunoglobulin G (immunology)
• Injections, Intradermal
• Microinjections
• Needles
• Oligodeoxyribonucleotides (administration & dosage)
• Poliovirus Vaccine, Inactivated (administration & dosage, immunology)
• Rats
• Rats, Wistar