Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid.
IL-12 plays a central role in both innate and acquired immunity and has been demonstrated to potentiate the protective immunity in several experimental vaccines. However, in this study, we show that IL-12 can be detrimental to the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associated with marked reduction of specific T cell proliferation and Ab responses. A single dose of pIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-gamma. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses, and thus its application as a vaccine adjuvant should be carefully evaluated.
Chen
H W
HW
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Pan
C H
CH
Huan
H W
HW
Liau
M Y
MY
Chiang
J R
JR
Tao
M H
MH
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D004672:Encephalitis, Japanese / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007111:Immunity, Cellular / Q000235:genetics; D007115:Immunization Schedule; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000009:adverse effects / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000235:genetics; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000008:administration & dosage* / Q000009:adverse effects; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000276:immunology
D000914:Antibodies, Viral; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D022321:Japanese Encephalitis Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma