Infectivity-enhancing antibodies to Ebola virus glycoprotein.
Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the GP. Substantially weaker enhancement was observed with antiserum to the GP of the Reston strain, which is much less pathogenic in humans than the Ebola Zaire and Sudan viruses. The enhancing activity was abolished by heat but was increased in the presence of complement system inhibitors, suggesting that heat-labile factors other than the complement system are required for this effect. We also generated an anti-Zaire GP monoclonal antibody that enhanced viral infectivity and another that neutralized it, indicating the presence of distinct epitopes for these properties. Our findings suggest that antibody-dependent enhancement of infectivity may account for the extreme virulence of the virus. They also raise issues about the development of Ebola virus vaccines and the use of passive prophylaxis or therapy with Ebola virus GP antibodies.
Takada
A
A
Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Watanabe
S
S
Okazaki
K
K
Kida
H
H
Kawaoka
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D029043:Ebolavirus / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D013045:Species Specificity; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014764:Viral Proteins; D014774:Virulence
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D014764:Viral Proteins; C110613:secreted glycoprotein, Ebola virus