Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

Joshua M. DiNapoli, Alexander Kotelkin, Lijuan Yang, Subbiah Elankumaran, Brian R. Murphy, Siba K. Samal, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002-2003 high-lighted 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.

Original languageEnglish (US)
Pages (from-to)9788-9793
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number23
DOIs
StatePublished - Jun 5 2007
Externally publishedYes

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Severe Acute Respiratory Syndrome
Newcastle disease virus
Host Specificity
Coronavirus
Immunization
Vaccines
Viruses
Avulavirus
Coronavirus Spike Glycoproteins
SARS Virus
Disease Vectors
Cercopithecus aethiops
Lung
Human Development
Neutralizing Antibodies
Respiratory System
Primates
Disease Outbreaks
Immunity
Antigens

Keywords

  • Monkey
  • Respiratory tract
  • Severe acute respiratory syndrome (SARS)

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens. / DiNapoli, Joshua M.; Kotelkin, Alexander; Yang, Lijuan; Elankumaran, Subbiah; Murphy, Brian R.; Samal, Siba K.; Collins, Peter L.; Bukreyev, Alexander.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 23, 05.06.2007, p. 9788-9793.

Research output: Contribution to journalArticle

DiNapoli, Joshua M. ; Kotelkin, Alexander ; Yang, Lijuan ; Elankumaran, Subbiah ; Murphy, Brian R. ; Samal, Siba K. ; Collins, Peter L. ; Bukreyev, Alexander. / Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 23. pp. 9788-9793.
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