Regulation of DNA-raised immune responses by cotransfected interferon regulatory factors.
Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold. Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased towards type 1 immune responses and the production of gamma interferon. Following gene gun bombardments of DNA, both were biased towards type 2 immune responses and the production of interleukin-4. The biases of the T-cell responses towards type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.
Sasaki
Shin
S
Division of Microbiology and Immunology, Yerkes National Primate Research Center and Vaccine Research Center, Emory University School of Medicine, 954 Gatewood Road, Atlanta, GA 30329, USA.
Amara
Rama Rao
RR
Yeow
Wen-Shuz
WS
Pitha
Paula M
PM
Robinson
Harriet L
HL
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D050856:Interferon Regulatory Factor-1; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004268:DNA-Binding Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D050856:Interferon Regulatory Factor-1; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494258:Irf1 protein, mouse; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D009698:Nucleoproteins; D010750:Phosphoproteins; D014157:Transcription Factors; D019444:Vaccines, DNA