Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge.
We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/DeltaF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/DeltaF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/DeltaF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.
Bukreyev
Alexander
A
National Institute of Allergy and Infectious Diseases, Building 50, Room 6505, NIAID, National Institutes of Health, 50 South Dr. MSC 8007, Bethesda, MD 20892-8007, USA. abukreyev@nih.gov
Marzi
Andrea
A
Feldmann
Friederike
F
Zhang
Liqun
L
Yang
Lijuan
L
Ward
Jerrold M
JM
Dorward
David W
DW
Pickles
Raymond J
RJ
Murphy
Brian R
BR
Feldmann
Heinz
H
Collins
Peter L
PL
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D001769:Blood / Q000821:virology; D001835:Body Weight; D002460:Cell Line; D002522:Chlorocebus aethiops; D046129:Ebola Vaccines / Q000235:genetics* / Q000276:immunology*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D006801:Humans; D008168:Lung / Q000821:virology; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010224:Parainfluenza Virus 3, Human / Q000235:genetics* / Q000276:immunology*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*; D014771:Virion / Q000648:ultrastructure
D000914:Antibodies, Viral; D046129:Ebola Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus