title: Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus.
abstract: Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is, however, problematic in emergency situations, e.g. during outbreaks in poultry, as there are currently no mass application methods to effectively vaccinate large numbers of birds within a short period of time. To evaluate the suitability of needle-free pulmonary immunization for mass vaccination of poultry against HPAI H5N1, we performed a proof-of-concept study in which we investigated whether non-adjuvanted spray-freeze-dried (SFD) whole inactivated virus (WIV) can be used as a dry powder aerosol vaccine to immunize chickens. Our results show that chickens that received SFD-WIV vaccine as aerosolized powder directly at the syrinx (the site of the tracheal bifurcation), mounted a protective antibody response after two vaccinations and survived a lethal challenge with HPAI H5N1. Furthermore, both the number of animals that shed challenge virus, as well as the level of virus shedding, were significantly reduced. Based on antibody levels and reduction of virus shedding, pulmonary vaccination with non-adjuvanted vaccine was at least as efficient as intratracheal vaccination using live virus. Animals that received aerosolized SFD-WIV vaccine by temporary passive inhalation showed partial protection (22% survival) and a delay in time-to-death, thereby demonstrating the feasibility of the method, but indicating that the efficiency of vaccination by passive inhalation needs further improvement. Altogether our results provide a proof-of-concept that pulmonary vaccination using an SFD-WIV powder vaccine is able to protect chickens from lethal HPAI challenge. If the efficacy of pulmonary vaccination by passive inhalation can be improved, this method might be suitable for mass application.
authors.affiliation: Central Veterinary Institute of Wageningen University and Research Centre, P.O. Box 65, 8200 AB Lelystad, The Netherlands. Electronic address: ben.peeters@wur.nl.
authors.forename: Ben
authors.initials: B
authors.lastname: Peeters
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Wouter F
authors.initials: WF
authors.lastname: Tonnis
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Senthil
authors.initials: S
authors.lastname: Murugappan
authors.affiliation: Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, Faculty of Veterinary Medicine, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Rottier
authors.affiliation: Central Veterinary Institute of Wageningen University and Research Centre, P.O. Box 65, 8200 AB Lelystad, The Netherlands.
authors.forename: Guus
authors.initials: G
authors.lastname: Koch
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: University Medical Center Groningen, Department of Medical Microbiology, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002645:Chickens / Q000276:immunology*; D005612:Freeze Drying; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000517:prevention & control*; D011208:Powders; D014611:Vaccination / Q000379:methods*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000336:Aerosols; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D011208:Powders; D015164:Vaccines, Inactivated
keywords: Avian flu; Inhalation; Mass vaccination; Poultry vaccine; Powder vaccine