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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Electroporation / methods
  • Electroporation / standards
  • Female
  • Immunoglobulin G / blood
  • Injections
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Plasmids / administration & dosage
  • Plasmids / immunology
  • Skin / immunology*
  • Spleen / immunology*
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology*

Substances

  • Immunoglobulin G
  • Vaccines, DNA