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

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• 作者：Pim Schipper^a ; ^{p.schipper@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author} ; Koen van der Maaden^a ; ^{k.van.der.maaden@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author} ; Stefan Romeijn^a ; ^{romeijn@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author} ; Cees Oomens^b ; ^{c.w.j.oomens@tue.nl" class="auth_mail" title="E-mail the corresponding author} ; Gideon Kersten^a ; ^c ; ^{gideon.kersten@intravacc.nl" class="auth_mail" title="E-mail the corresponding author} ; Wim Jiskoot^a ; ^{w.jiskoot@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author} ; Joke Bouwstra^a ; ^{bouwstra@lacdr.leidenuniv.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CpG ; CpG oligodeoxynucleotide 1826 ; DU ; D-antigen units ; ID ; intradermal ; ID-bolus ; intradermal bolus immunization ; IM ; intramuscular ; IM-bolus ; intramuscular bolus immunization ; IPV ; inactivated polio vaccine ; IPV1 ; inactivated polio vaccine serotype 1 ; OPV ; oral polio vaccine ; PBS ; phosphate buffered saline ; VN ; virus neutralization
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 November 2016
• 年：2016
• 卷：242
• 期：Complete
• 页码：141-147
• 全文大小：474 K

文摘

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 150 μm 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.