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

doi:10.1073/pnas.0703584104

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

*Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
^†University of Maryland, College Park, MD 20742

Communicated by Robert M. Chanock, National Institutes of Health, Bethesda, MD, April 24, 2007 (received for review January 22, 2007)

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.

Footnotes

^‡To whom correspondence should be addressed at:
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6505, Bethesda, MD 20892.
E-mail: ab176v{at}nih.gov
Author contributions: J.M.D., B.R.M., S.K.S., P.L.C., and A.B. designed research; J.M.D., A.K., L.Y., S.E., S.K.S., and A.B. performed research; S.K.S. contributed new reagents/analytic tools; J.M.D., B.R.M., S.K.S., P.L.C., and A.B. analyzed data; and J.M.D., B.R.M., P.L.C., and A.B. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0703584104/DC1.
Abbreviations:

AGM,

African green monkeys;

BC,

Beaudette C;

HAI,

hemagglutination inhibition;

i.n.,

intranasal;

i.t.,

intratracheal;

MVA,

modified vaccinia Ankara;

NDV,

Newcastle disease virus;

PBMC,

peripheral blood mononuclear cell;

SARS-CoV,

severe acute respiratory syndrome-associated coronavirus;

TCID50,

tissue culture 50% infectious dose.