Development of a preventive vaccine for Ebola virus infection in primates.
Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates.
Sullivan
N J
NJ
Vaccine Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sanchez
A
A
Rollin
P E
PE
Yang
Z Y
ZY
Nabel
G J
GJ
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D004279:DNA, Viral / Q000276:immunology*; D015023:Democratic Republic of the Congo; D029043:Ebolavirus; D005822:Genetic Vectors / Q000276:immunology; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D007117:Immunization, Secondary; D008252:Macaca fascicularis; D051379:Mice; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D004279:DNA, Viral; D019590:Nucleocapsid Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C113189:envelope glycoprotein, Ebola virus; C113190:nucleocapsid protein, Ebola virus