title: Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine.
abstract: BACKGROUND
  Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI) H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α) and chicken interleukin-18 (chIL-18) as natural immunomodulators.
  
  
  RESULTS
  Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens.
  
  
  CONCLUSIONS
  Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.
authors: College of Veterinary Medicine and Bio-Safety Research Institute, Jeonju 561-756, Republic of Korea.
authors: Md Masudur
authors: MM
authors: Rahman
authors: Erdenebileg
authors: E
authors: Uyangaa
authors: Young Woo
authors: YW
authors: Han
authors: Seong Bum
authors: SB
authors: Kim
authors: Jin Hyoung
authors: JH
authors: Kim
authors: Jin Young
authors: JY
authors: Choi
authors: Seong Kug
authors: SK
authors: Eo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D053127:Influenza A Virus, H9N2 Subtype; D005585:Influenza in Birds / Q000517:prevention & control*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology*; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D016898:Interferon-alpha; D020382:Interleukin-18; D015164:Vaccines, Inactivated; D014765:Viral Vaccines