Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA).
Vaccination with plasmids encoding an antigen of interest (DNA vaccination) is a new strategy to achieve effective immunization against many agents. DNA vaccination can be ameliorated by co-administration of plasmids encoding a cytokine. Thus far, only plasmids encoding soluble cytokines have been used for this purpose. However, these plasmids can induce release of cytokines into the circulation and could potentially cause many undesirable effects. We undertook this study to determine whether membrane-bound cytokines, which would restrict their localization at the site of administration, can act as immunoadjuvants. We and others have previously shown that plasmids encoding soluble IL-4 and IL-12 are effective adjuvants for DNA vaccination. In this study, we demonstrate that DNA co-vaccination with membrane-bound IL-4 (mbIL-4) or membrane-bound IL-12 (mbIL-12) both enhance anti-CEA immunity, as detected by in vitro and in vivo assays. Mice co-injected with plasmids encoding CEA and either type of membrane-bound cytokine rejected transplanted CEA-positive tumor cells strongly. Notably, unlike secreted IL-4, mbIL-4 was the most effective adjuvant for anti-tumor immunity. This study demonstrates that membrane-bound cytokines are suitable adjuvants for DNA vaccination.
Department of Laboratory Medicine and Pathobiology, St. Micheal's Hospital and University of Toronto, 30 Bond Street, Toronto, Ont., Canada M5B 1W8.
Rabindranath
R
Chakrabarti
Yigang
Y
Chang
Keli
K
Song
Gerald J
GJ
Prud'homme
D000276:Adjuvants, Immunologic; D000818:Animals; D019556:COS Cells; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism; D002522:Chlorocebus aethiops; D007114:Immunization; D018664:Interleukin-12 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D019444:Vaccines, DNA / Q000235:genetics*
D000276:Adjuvants, Immunologic; D002272:Carcinoembryonic Antigen; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4