Ebola GP-Specific Monoclonal Antibodies Protect Mice and Guinea Pigs from Lethal Ebola Virus Infection

被引:80
作者
Qiu, Xiangguo [1 ]
Fernando, Lisa [1 ]
Melito, P. Leno [1 ]
Audet, Jonathan [1 ,2 ]
Feldmann, Heinz [1 ,2 ]
Kobinger, Gary [1 ,2 ,3 ]
Alimonti, Judie B. [1 ,2 ]
Jones, Steven M. [1 ,2 ,3 ]
机构
[1] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada
[2] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada
[3] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada
来源
PLOS NEGLECTED TROPICAL DISEASES | 2012年 / 6卷 / 03期
关键词
HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; MOUSE MODEL; POSTEXPOSURE TREATMENT; PASSIVE TRANSFER; GENE-EXPRESSION; GLYCOPROTEIN GP; EPITOPES; CYTOTOXICITY; REPLICATION;
D O I
10.1371/journal.pntd.0001575
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3-4 MAbs to test their protection against a lethal challenge with mouse-or guinea pig-adapted EBOV. Each of the 8 MAbs (100 mu g) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3-4 MAbs completely protected the majority of animals, while administration at 2-3 dpi achieved 50-100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.
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页数:8
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