Abstract
DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.
Highlights
Introduction of DNA VaccinesAlmost two decades ago, it was reported that plasmid DNA could induce adaptive immune responses against plasmid-encoded antigens [1], indicating it could be used in novel therapeutic applications as a human vaccine for the prevention of various pathogen infections [2], autoimmunity [3], allergy [4], neurological disorders [5], and cancer [6]
Constitutive active forms of interferon regulatory factor 3 (IRF3) and IRF7 were evaluated as DNA vaccine adjuvants and elicited both humoral and cellular immune responses to protect against vaccinia virus infection [74]
These results suggest that TANK-binding kinase 1 (TBK1) genetic adjuvant improves the immunogenicity of DNA vaccines, at least in anti-malarial immunogenicity
Summary
It was reported that plasmid DNA could induce adaptive immune responses against plasmid-encoded antigens [1], indicating it could be used in novel therapeutic applications as a human vaccine for the prevention of various pathogen infections [2], autoimmunity [3], allergy [4], neurological disorders [5], and cancer [6]. Double-stranded DNA (dsDNA) is a critical ligand of the STING-TBK1 signaling cascade [9] These results indicate that dsDNA-induced innate immune signaling lead to induction of DNA-encoded antigen specific adaptive immune responses, like an adjuvant. Demonstrated that the intramuscular administration of plasmid DNA encoding influenza viral protein induced encoded antigen-specific cytotoxic T lymphocyte (CTL) responses, which protected against lethal influenza virus infection [1]. Plasmid DNA integration was lower than the natural rate of mutation in mammalian genomes [14] Another safety concern is development of anti-DNA antibodies, associated with autoimmune disorders [15].
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