Anti-Ebola GP monoclonal antibodies protect mice and guinea pigs against lethal ebola virus challenge (105.29)

Abstract

Abstract Introduction: Ebola virus (EBOV) causes acute hemorrhagic fever in humans and nonhuman 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 a mouse and guinea pig model. Methods: Healthy 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 dose of mouse- or guinea pig-adapted EBOV. Results: Each of the 8 mAbs (100 microgram) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven mAbs were effective 2 days post-challenge (dpc), with 1 mAb demonstrating partial protection 3 dpc. Furthermore, 4 mAbs achieved 70-100% protection with a single dose of 12.5 microgram at 1 dpc. In the guinea pig model each mAb showed partial protection 1 dpc, 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 2-3 dpc achieved 50-100% protection. Conclusions: Our data suggests the mAbs generated are capable of protecting both animal models against a lethal challenge of Ebola virus. These results indicate that mAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.