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



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.



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).



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.
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
P
Schipper
Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Koen
K
van der Maaden
Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Stefan
S
Romeijn
Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Cees
C
Oomens
Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.|Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
Gideon
G
Kersten
Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Wim
W
Jiskoot
Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands. bouwstra@lacdr.leidenuniv.nl.
Joke
J
Bouwstra
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007271:Injections, Intradermal / Q000379:methods; D007273:Injections, Intramuscular / Q000379:methods; D008845:Microinjections / Q000379:methods; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011054:Poliovirus Vaccine, Inactivated
dose sparing; hollow microneedles; inactivated polio vaccine; intradermal immunization; poliomyelitis