title: A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.
abstract: Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy.
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Röhrs
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Donata
authors.initials: D
authors.lastname: Kalthoff
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Südufer 10, 17493 Greifswald - Insel Riems, Germany. Electronic address: martin.beer@fli.bund.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002645:Chickens; D005260:Female; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics; D007252:Influenza Vaccines / Q000008:administration & dosage*; D005585:Influenza in Birds / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D012367:RNA, Viral / Q000302:isolation & purification; D017384:Sequence Deletion; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D012367:RNA, Viral; D009439:Neuraminidase
keywords: Avian influenza virus; Early onset of protection; H5N1; Neuraminidase