title: Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens.
abstract: Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271-330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans.
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States.
authors: Shin-Hee
authors: SH
authors: Kim
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States.
authors: Anandan
authors: A
authors: Paldurai
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States.
authors: Sa
authors: S
authors: Xiao
authors: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United States.
authors: Peter L
authors: PL
authors: Collins
authors: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD, United States. Electronic address: ssamal@umd.edu.
authors: Siba K
authors: SK
authors: Samal
mesh_terms: D000818:Animals; D002645:Chickens; D004337:Drug Carriers / Q000008:administration & dosage*; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control*; D009522:Newcastle disease virus / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus
keywords: H5N1 highly virulent avian influenza virus; Hemagglutinin; Newcastle disease virus; Vectored vaccine