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通过中空微针进行微量注射递送的佐剂灭活脊髓灰质炎疫苗的深度依赖性皮内免疫原性的测定。

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

作者信息

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

机构信息

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

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

出版信息

Pharm Res. 2016 Sep;33(9):2269-79. doi: 10.1007/s11095-016-1965-6. Epub 2016 Jun 17.

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.

摘要

目的

本研究旨在通过中空微针(HMN)进行深度控制的微量注射,研究灭活脊髓灰质炎疫苗(IPV)的皮内免疫原性与深度的关系,并研究用CpG寡脱氧核苷酸1826(CpG)或霍乱毒素(CT)佐剂的IPV免疫对抗体反应的增强作用。

方法

设计了一种新型的HMN注射器,以实现深度和体积控制的微量注射。该注射器用于对大鼠进行皮内免疫,注射单价1型IPV(IPV1),注射深度范围为50至550μm,对于用CpG和CT佐剂免疫的情况,注射深度为400μm,并与肌肉注射进行比较。

结果

该注射器能够在预定的注射深度(50 - 900μm)、体积(1 - 100μL)和速率(高达60μL/分钟)下准确地对大鼠皮肤进行微量注射,体积损失最小(±1 - 2%)。HMN介导的皮内免疫产生的IgG和病毒中和抗体滴度与传统肌肉注射相似。未观察到IgG滴度随注射深度的变化,但在CpG和CT佐剂组中IgG滴度显著增加(7倍)。

结论

IPV1的皮内免疫原性不受注射深度的影响。CpG和CT是皮内和肌肉免疫的有效佐剂,通过HMN单次微创皮内注射即可实现有效疫苗接种。

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