title: MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens.
abstract: Chickens lack the retinoic acid-inducible gene I (RIG-I) and sense avian influenza virus (AIV) infections by means of the melanoma differentiation-associated gene 5 product (chMDA5). Plasmid-driven expression of the N-terminal half of chMDA5 containing the caspase activation and recruitment domains [chMDA5(1-483)] triggers interferon-β responses in chicken cells. We hypothesized that mimicking virus infection by chMDA5(1-483) expression may enhance vaccine-induced adaptive immunity. In order to test this, the potential genetic adjuvant properties of chMDA5(1-483) were evaluated in vivo in combination with a suboptimal quantity of a plasmid DNA vaccine expressing haemagglutinin (HA) of H5N1 AIV. Co-administration of the HA plasmid with plasmid DNA for chMDA5(1-483) expression resulted in approximately 10-fold higher HA-specific antibody responses than injection of the HA plasmid mixed with empty vector DNA as control. Accordingly, compared with HA DNA vaccination alone, the chMDA5(1-483)-adjuvanted HA DNA vaccine mediated enhanced protection against a lethal H5N1 challenge infection in chickens, with reduced clinical signs and cloacal virus shedding. These data demonstrate that innate immune activation by expression of signaling domains of RIG-I-like receptors can be exploited to enhance vaccine efficacy.
authors.affiliation: Research Department, Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Liniger
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
mesh_terms: D000818:Animals; D002645:Chickens / Q000821:virology*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000302:isolation & purification*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D005585:Influenza in Birds / Q000235:genetics / Q000517:prevention & control* / Q000821:virology; D010957:Plasmids; D012367:RNA, Viral / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D007252:Influenza Vaccines; D012367:RNA, Viral; D019444:Vaccines, DNA; D053487:DEAD-box RNA Helicases