[Source: Journal of Virology, full page: (LINK). Abstract, edited.]
Equine-origin immunoglobulin fragments protects nonhuman primates from Ebola virus disease
Hualei Wang, Gary Wong, Wenjun Zhu, Shihua He, Yongkun Zhao, Feihu Yan, Md Niaz Rahim, Yuhai Bi, Zirui Zhang, Keding Cheng, Hongli Jin, Zengguo Cao, Xuexing Zheng, Weiwei Gai,Jieying Bai, Weijin Chen, Yong Zou, Yuwei Gao, George F Gao, Songtao Yang, Xianzhu Xia, Xiangguo Qiu
Ebola virus (EBOV) infections result in aggressive hemorrhagic fever in humans with fatality rates reaching 90%, with no licensed, specific therapeutics to treat ill patients. Advances over the past 5 years have firmly established monoclonal antibody (mAb)-based products as the most promising therapeutics for treating EBOV infections, but production is costly, quantities are limited, and thus mAbs are not the best candidates for mass use in the case of an epidemic. To address this need, we generated EBOV-specific polyclonal immunoglobulin fragments F(ab’)2 from horses hyperimmunized with an EBOV vaccine. The F(ab’)2 was found to potently neutralize West and Central African EBOV in vitro. Treatment of nonhuman primates (NHPs) with seven doses of 100mg/kg F(ab’)2 beginning at 3 or 5 days post-infection (dpi) resulted in 100% survival. Notably, NHPs that initiated treatment at 5 dpi were already highly viremic with observable signs of EBOV disease, demonstrating that F(ab’)2 was still effective as a therapeutic even in symptomatic patients. These results show that F(ab’)2 should be accelerated for clinical testing in preparation of future EBOV outbreaks and epidemics.
Ebola is one of the deadliest viruses to humans. It has been over 40 years since Ebola was first reported, but no cure is available. Research breakthroughs over the last 5 years have shown that monoclonal antibodies (mAbs) constitute an effective therapy for Ebola. However, mAbs are expensive, difficult to produce in large amounts and therefore may only play a limited role during an epidemic. A cheaper alternative is required, especially since Ebola is endemic in several third-world countries with limited medical resources. Here, we used a standard protocol to produce large amounts of antisera fragments (F(ab’)2) from horses vaccinated with an Ebola vaccine, and tested its protectiveness in monkeys. We showed that F(ab’)2 was effective in 100% of monkeys even after these animals were visibly ill with Ebola. Thus, F(ab’)2 could be a very good option for large-scale treatments of patients and should be advanced to clinical testing.
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Keywords: Ebola; Serotherapy; Animal models.