title: The virus-induced signaling adaptor molecule enhances DNA-raised immune protection against H5N1 influenza virus infection in mice.
abstract: As an adaptor molecule in the retinoic acid-inducible gene-I (RIG-I) signaling pathway, the virus-induced signaling adaptor (VISA) molecule activates NF-κB and IRF3 and thereby leads to the production of type I interferons (IFNs). To explore the potential of VISA as a genetic adjuvant for DNA vaccines, a eukaryotic expression plasmid, pVISA, was generated by cloning the VISA gene into the pVAX1vector. For comparison, the pTRIF plasmid was similarly constructed, encoding the known genetic adjuvant TRIF (TIR-domain-containing adapter-inducing interferon-β), an adapter in the Toll-like receptor (TLR) signaling pathway. Mice were immunized with the chimeric DNA vaccine pHA/NP(147-155), which encodes the HA (hemagglutinin) fused with NP (nucleoprotein) CTL epitope (NP(147-155)) of H5N1 influenza virus, either alone or in combination with pVISA or pTRIF. Antigen-specific immune responses were examined in immunized mice. Our results demonstrate that co-immunization of the pHA/NP(147-155) plasmid with the VISA adjuvant augmented DNA-raised cellular immune responses and provided protection against H5N1 influenza virus challenge in mice. In addition, our data suggest that VISA acts as a stronger adjuvant for DNA immunization than TRIF. We conclude that co-inoculation with a vector expressing the adaptor molecule VISA enhanced the protective immunity against H5N1 infection induced by pHA/NP(147-155) and that VISA could be developed as a novel genetic adjuvant for DNA vaccines.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei Province, Wuhan 430072, PR China.
authors.forename: Mengcheng
authors.initials: M
authors.lastname: Luo
authors.forename: Xiao
authors.initials: X
authors.lastname: Qu
authors.forename: Ruangang
authors.initials: R
authors.lastname: Pan
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Zishu
authors.initials: Z
authors.lastname: Pan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000008:administration & dosage* / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000008:administration & dosage* / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; C048842:NP protein, Influenza A virus; C476286:Ticam1 protein, mouse; C512612:MAVS protein, mouse