Interferon regulatory factor‐1 acts as a powerful adjuvant in tat DNA based vaccination

Abstract

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.

Molecular mechanisms for enhanced DNA vaccine immunogenicity

“…MDA5, a RIG-I like dsRNA receptor, enhanced DNA vaccination against H5N1 influenza virus infection in chickens [105]. Recent studies showed that a plasmid expressing interferon regulatory transcription factor (IRF), enhanced CTL and IFN-γ responses against an HIV-1 Tat vaccine [106], whereas no effects were observed with IRF3 or IRF7 plasmids [106]. NF-κB is a master innate immune regulator.…”

Influenza vaccine: Where are we and where do we go?

“…Also, constitutive active forms of IRF3 and IRF7, as DNA vaccine adjuvants, elicit both humoral and cellular immune responses against virus infection . In addition, studies showed that DNA binding domain‐lacked IRF1 (ΔIRF1) genetic adjuvant enhanced cellular immune responses …”

Biomaterials at the interface of nano- and micro-scale vector–cellular interactions in genetic vaccine design

“…These adjuvants operate by controlling (or inducing) the production of immunogenic cytokines and chemokines. There has been significant commercial development of transcription factor-based vectors including TBK1 (TANK-binding kinase 1; general immunopotentiator 71 ; InvivoGen), IRF1 (interferon regulatory factor 1; increases humoral responses 72 , limited cell-mediated response 69 ; InvivoGen), IRF3 (increases cell-mediated responses 72 ; InvivoGen), and chimeric IRF7/3 (increases both cell-mediated and humoral responses 70 ; InvivoGen).…”