title: Oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 enhances the alleviation of clinical signs caused by respiratory infection with avian influenza virus H9N2.
abstract: The combined use of cytokines has shown synergistic and/or additive effects in controlling several viral infections of livestock animals. However, little is known concerning the practical use of chicken cytokine combinations to control avian diseases. Here, we investigated the antiviral efficacy of oral co-administration of chicken interferon-α (chIFN-α) and chicken interleukin-18 (chIL-18) using attenuated Salmonella enterica serovar Typhimurium in chickens infected with avian influenza virus (AIV) H9N2. Our results demonstrate that oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 produced a greater alleviation of clinical signs caused by respiratory infection with AIV H9N2 in chickens, when compared to administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18 alone. Mortality, clinical symptom severity, and feed and water intake were used to access treatment effectiveness. This enhancement of antiviral immunity was further confirmed by evidence of reduced rectal shedding and decreased replication of AIV H9N2 in several different tissues of challenged chickens including trachea, lung, cecal tonsil, and brain. Furthermore, oral co-administration of chIFN-α and chIL-18 more efficiently modulated the immune responses of chickens against AIV H9N2 by enhancing both humoral and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results suggest that the combined administration of two chicken cytokines, chIFN-α and chIL-18, using attenuated S. enterica serovar Typhimurium as an oral carrier, provides an effective means for controlling respiratory disease caused by AIV H9N2 infection.
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Jeonju 561-756, Republic of Korea.
authors.forename: Md Masudur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Erdenebileg
authors.initials: E
authors.lastname: Uyangaa
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Han
authors.forename: Seong Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Seong Kug
authors.initials: SK
authors.lastname: Eo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use*; D002645:Chickens / Q000276:immunology* / Q000821:virology; D006385:Hemagglutination Inhibition Tests; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology* / Q000502:physiology; D005585:Influenza in Birds / Q000188:drug therapy* / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000276:immunology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000276:immunology; D012486:Salmonella typhimurium; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D016898:Interferon-alpha; D020382:Interleukin-18; D011994:Recombinant Proteins