Open AccessNewcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens
Author(s) -
Joshua DiNapoli,
Alexander Kotelkin,
Lijuan Yang,
Subbiah Elankumaran,
Brian R. Murphy,
Siba K. Samal,
Peter L. Collins,
Alexander Bukreyev
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0703584104
Subject(s) - virology , virus , biology , viral shedding , vaccination , plaque forming unit , immunization , newcastle disease , immunity , viral vector , vector (molecular biology) , immune system , immunology , medicine , recombinant dna , biochemistry , gene
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.