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

✍ Scribed by Xin Guan; Makiya Nishikawa; Seiji Takemoto; Yuji Ohno; Tomoya Yata; Yoshinobu Takakura

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 466 KB
• Volume: 12
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1432

✦ Synopsis

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. Copyright © 2010 John Wiley & Sons, Ltd.