Successful Treatment of Ebola Virus-Infected Cynomolgus Macaques with Monoclonal Antibodies

被引:239
作者
Qiu, Xiangguo [1 ]
Audet, Jonathan [2 ]
Wong, Gary [2 ]
Pillet, Stephane [1 ]
Bello, Alexander [2 ]
Cabral, Teresa [1 ]
Strong, Jim E. [1 ]
Plummer, Frank [1 ]
Corbett, Cindy R. [1 ,2 ,3 ]
Alimonti, Judie B. [1 ,2 ]
Kobinger, Gary P. [1 ,2 ,3 ]
机构
[1] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada
[2] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J9, Canada
[3] Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0T5, Canada
关键词
ACTIVATED PROTEIN-C; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; ZAIRE-EBOLAVIRUS; MOUSE MODEL; VACCINE; MONKEYS; PROPHYLAXIS; IMMUNOGLOBULIN;
D O I
10.1126/scitranslmed.3003876
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ebola virus (EBOV) is considered one of the most aggressive infectious agents and is capable of causing death in humans and nonhuman primates (NHPs) within days of exposure. Recent strategies have succeeded in preventing acquisition of infection in NHPs after treatment; however, these strategies are only successful when administered before or minutes after infection. The present work shows that a combination of three neutralizing monoclonal antibodies (mAbs) directed against the Ebola envelope glycoprotein (GP) resulted in complete survival (four of four cynomolgus macaques) with no apparent side effects when three doses were administered 3 days apart beginning at 24 hours after a lethal challenge with EBOV. The same treatment initiated 48 hours after lethal challenge with EBOV resulted in two of four cynomolgus macaques fully recovering. The survivors demonstrated an EBOV-GP-specific humoral and cell-mediated immune response. These data highlight the important role of antibodies to control EBOV replication in vivo, and support the use of mAbs against a severe filovirus infection.
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页数:12
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