Repeated fractional intradermal dosing of an inactivated polio vaccine by a single hollow microneedle leads to superior immune responses

J Control Release. 2016 Nov 28;242:141-147. doi: 10.1016/j.jconrel.2016.07.055. Epub 2016 Aug 2.


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.

Keywords: Adjuvant; Dose-sparing; Fractional dose; Hollow microneedles; Inactivated polio vaccine; Intradermal immunization; Poliomyelitis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Poliovirus Vaccine, Inactivated / immunology
  • Rats
  • Rats, Wistar


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