Interferon regulatory factor-1 acts as a powerful adjuvant in tat DNA based vaccination.
Genetic vaccines are safe cost-effective approaches to immunization but DNA immunization is an inefficient process. There is, therefore, a pressing need for adjuvants capable of enhancing the immunogenicity and effectiveness of these vaccines. This is particularly important for diseases for which successful vaccines are still lacking, such as cancer and infectious diseases including HIV-1/AIDS. Here we report an approach to enhance the immunogenicity of DNA vaccines involving the use of transcription factors of the Interferon regulatory factor (IRF) family, specifically IRF-1, IRF-3, and IRF-7 using the tat gene as model antigen. Balb/c mice were immunized by three intramuscular inoculations, using a DNA prime-protein boost protocol, with a DNA encoding tat of HIV-1 and the indicated IRFs and immune responses were compared to those induced by vaccination with tat DNA alone. In vivo administration of plasmid DNA encoding IRF-1, or a mutated version of IRF-1 deleted of the DNA-binding domain, enhanced Tat-specific immune responses and shifted them towards a predominant T helper 1-type immune response with increased IFN-gamma production and cytotoxic T lymphocytes responses. Conversely, the use of IRF-3 or IRF-7 did not affect the tat-induced responses. These findings define IRF-1 and its mutated form as efficacious T helper 1-inducing adjuvants in the context of tat-based vaccination and also providing a new promising candidate for genetic vaccine development.
Castaldello
Arianna
A
Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Padova, Italy.
Sgarbanti
Marco
M
Marsili
Giulia
G
Brocca-Cofano
Egidio
E
Remoli
Anna Lisa
AL
Caputo
Antonella
A
Battistini
Angela
A
D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007114:Immunization; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D050856:Interferon Regulatory Factor-1; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D019444:Vaccines, DNA; D054322:tat Gene Products, Human Immunodeficiency Virus; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases