title: Live Attenuated Influenza H7N3 Vaccine is Safe, Immunogenic and Confers Protection in Animal Models.
abstract: BACKGROUND
  In 2003 the outbreak of highly pathogenic H7 avian influenza occurred in the Netherlands. The avian H7 virus causing the outbreak was also detected in humans; one person died of pneumonia and acute respiratory distress syndrome. Our paper describes preclinical studies of a H7N3 live attenuated influenza A vaccine (LAIV) candidate in various animal models.
  
  
  OBJECTIVE
  To study safety, immunogenicity and protection of H7N3 LAIV candidate in mice, ferrets and chickens.
  
  
  METHODS
  The vaccine was generated by a classical reassortment between low pathogenicity A/mallard/Netherlands/00 (H7N3) virus and A/Leningrad4/17/57 (H2N2) master donor virus (MDV).
  
  
  RESULTS
  Immunogenicity was found that H7N3 LAIV was similar to the MDV in terms of replication in the respiratory organs of mice and failed to replicate in mouse brains. One dose of a H7N3 LAIV elicited measurable antibody response and it was further boosted with a second vaccine dose. Immunization of mice with H7N3 LAIV provided protection against infection following a homologous challenge with wild type H7N3 virus. Attenuated phenotype of H7N3 LAIV has been confirmed in ferrets. Immunogenicity and protective efficacy of H7N3 LAIV in ferrets were also demonstrated. The vaccine protected animals from subsequent infection with wild type H7N3 virus. The results of histopathology study revealed that inoculation of H7N3 LAIV in ferrets did not cause any inflammation or destructive changes in lungs. Lack of H7N3 LAIV replication in chicken demonstrated complete safety of this preparation for poultry.
  
  
  CONCLUSIONS
  Results of our study suggest that new H7N3 LAIV candidate is safe, immunogenic and protects from homologues influenza virus infection in mice and ferrets.
authors: Department of Virology, Institute of Experimental Medicine RAMS, St. Petersburg, Russia.
authors: Andrey
authors: A
authors: Rekstin
authors: Department of Virology, Institute of Experimental Medicine RAMS, St. Petersburg, Russia.
authors: Yulia
authors: Y
authors: Desheva
authors: Department of Virology, Institute of Experimental Medicine RAMS, St. Petersburg, Russia.
authors: Irina
authors: I
authors: Kiseleva
authors: University of Pittsburg (Pittsburg, USA).
authors: Ted
authors: T
authors: Ross
authors: Southeast Poultry Research Laboratory (Athens, USA).
authors: David
authors: D
authors: Swayne
authors: Department of Virology, Institute of Experimental Medicine RAMS, St. Petersburg, Russia.
authors: Larisa
authors: L
authors: Rudenko
keywords: H7N3; influenza; live attenuated influenza vaccine; pre-pandemic vaccine.; preclinical studies