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J Gene Med. 2010 Mar;12(3):301-9. doi: 10.1002/jgm.1432.

Injection site-dependent induction of immune response by DNA vaccine: comparison of skin and spleen as a target for vaccination.

Author information

1
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

Abstract

BACKGROUND:

The antigen-specific immune response is dependent not only on the properties of the antigens, but also on their encounter with antigen-presenting cells. A previous study showed that the spleen produced a large amount of transgenes after direct tissue injection of plasmid DNA. In addition, the spleen is the largest organ in the lymphatic system and contains a variety of types of immune cells, including lymphocytes, macrophages and dendritic cells. Thus, it can be a promising target for DNA vaccination.

METHODS:

Tissue-dependent properties of transgene expression were examined using a plasmid vector expressing firefly luciferase. Mice received injections of pCMV-Luc into the dorsal skin or spleen followed by electroporation, and the luciferase activity was measured 6 h after injection. Then, plasmids expressing a model antigen ovalbumin (pCMV-OVA) or its typical major histocompatibility complex class I-restricted epitope SIINFEKL (pPep-ER) were injected into C57BL/6 mice twice at an interval of 1 week. Seven days after the second immunization, OVA-specific humoral and cellular immune responses were evaluated.

RESULTS:

The spleen produced a larger amount of transgenes than the skin after direct tissue injection of plasmid DNA. However, intradermal injection of plasmid DNA resulted in a larger amount of OVA-specific antibodies and a greater cytotoxic T lymphocyte response compared to intrasplenic injection. In addition, intradermal immunization with either pCMV-OVA or pPep-ER generated more protective effects against EG7-OVA tumor challenge.

CONCLUSIONS:

The results obtained in the present study indicate that the spleen is unlikely to be a good target for immunization despite the presence of a large number of lymphocytes and efficient production of transgenes.

PMID:
20084616
DOI:
10.1002/jgm.1432
[Indexed for MEDLINE]

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