Protective efficacy of neutralizing antibodies against Ebola virus infection.
Ebola virus causes lethal hemorrhagic fever in humans and nonhuman primates, but no effective antiviral compounds are available for the treatment of this infection. The surface glycoprotein (GP) of Ebola virus is an important target of neutralizing antibodies. Although passive transfer of GP-specific antibodies has been evaluated in mouse and guinea pig models, protection was achieved only by treatment shortly before or after virus challenge. Using these animal models, we evaluated the protective efficacy of two monoclonal antibodies whose epitopes are distinct from those of the antibodies tested by others. Treatment of mice with these antibodies 2 days after challenge completely protected most of the animals; even treatment 3 or 4 days after challenge was partially effective. Although antibody treatment in the guinea pig model was not as effective as in the mouse model, single-dose treatment of guinea pigs 1 day before, or 1 or 2 days after challenge did protect some animals. Interestingly, the protective effects seen in these animal models did not correlate with the in vitro neutralizing activity of the antibodies, suggesting different mechanisms of the neutralization by these antibodies. These results underscore the potential therapeutic utility of monoclonal antibodies for postexposure treatment of Ebola virus infections.
Takada
Ayato
A
Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 060-0818, Japan. atakada@czc.hokudai.ac.jp
Ebihara
Hideki
H
Jones
Steven
S
Feldmann
Heinz
H
Kawaoka
Yoshihiro
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D007116:Immunization, Passive / Q000379:methods*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins