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Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles

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Abstract

Purpose

The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleotide 1826 (CpG) or cholera toxin (CT).

Methods

A novel applicator for HMN was designed to permit depth- and volume-controlled microinjections. The applicator was used to immunize rats intradermally with monovalent IPV serotype 1 (IPV1) at injection depths ranging from 50 to 550 μm, or at 400 μm for CpG and CT adjuvanted immunization, which were compared to intramuscular immunization.

Results

The applicator allowed accurate microinjections into rat skin at predetermined injection depths (50–900 μm), -volumes (1–100 μL) and -rates (up to 60 μL/min) with minimal volume loss (±1–2%). HMN-mediated intradermal immunization resulted in similar IgG and virus-neutralizing antibody titers as conventional intramuscular immunization. No differences in IgG titers were observed as function of injection depth, however IgG titers were significantly increased in the CpG and CT adjuvanted groups (7-fold).

Conclusion

Intradermal immunogenicity of IPV1 was not affected by injection depth. CpG and CT were potent adjuvants for both intradermal and intramuscular immunization, allowing effective vaccination upon a minimally-invasive single intradermal microinjection by HMN.

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Abbreviations

CpG:

CpG oligodeoxynucleotide 1826

CT:

Cholera toxin

DC:

Dendritic cell

DDC:

Dermal dendritic cell

H&E:

Hematoxylin and eosin

HMN:

Hollow microneedle

IPV:

Inactivated polio vaccine

IPV1:

Monovalent inactivated polio vaccine serotype 1

LC:

Langerhans cell

OPV:

Oral polio vaccine

PBS:

Phosphate buffered saline

TMB:

3,3′5,5′-tetramethylbenzidine

VN:

Virus neutralizing

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Heleen Kraan for contributions to analysis of IPV-specific IgG and VN responses, Raphael Zwier for contributions to the applicator design and Anne Römgens for contributions to discussions related to this study.

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Authors and Affiliations

  1. Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands

    Pim Schipper, Koen van der Maaden, Stefan Romeijn, Gideon Kersten, Wim Jiskoot & Joke Bouwstra

  2. Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands

    Cees Oomens

  3. Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands

    Gideon Kersten

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  1. Pim Schipper
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  2. Koen van der Maaden
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Corresponding author

Correspondence to Joke Bouwstra.

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Funding

This study was funded by the Dutch Technology Foundation STW, which is part of the Netherlands Organization for Scientific Research (NWO), and which is partly funded by the Ministry of Economic Affairs (project no. 11259).

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Schipper, P., van der Maaden, K., Romeijn, S. et al. Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles. Pharm Res 33, 2269–2279 (2016). https://doi.org/10.1007/s11095-016-1965-6

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  • DOI: https://doi.org/10.1007/s11095-016-1965-6

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