title: Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens.
abstract: The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002-2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARS-CoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: DiNapoli
authors.forename: Alexander
authors.initials: A
authors.lastname: Kotelkin
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Subbiah
authors.initials: S
authors.lastname: Elankumaran
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002522:Chlorocebus aethiops; D021821:Communicable Diseases, Emerging / Q000276:immunology / Q000517:prevention & control*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D009522:Newcastle disease virus / Q000276:immunology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D014765:Viral Vaccines