Injection site-dependent induction of immune response by DNA vaccine: comparison of skin and spleen as a target for vaccination.
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.
Guan
Xin
X
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Nishikawa
Makiya
M
Takemoto
Seiji
S
Ohno
Yuji
Y
Yata
Tomoya
T
Takakura
Yoshinobu
Y
D000818:Animals; D000917:Antibody Formation; D018274:Electroporation / Q000379:methods / Q000592:standards; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D007074:Immunoglobulin G; D019444:Vaccines, DNA