1. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection
- Author
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Xiangguo Qiu, Yuetao Li, Yuhai Bi, Jun Qian, Nan Li, Feihu Yan, Hang Chi, George F. Gao, Zengguo Cao, Tiecheng Wang, Gary P. Kobinger, Di Chu, Xianzhu Xia, Hongli Jin, Weiwei Gai, Weijin Chen, Songtao Yang, Yuwei Gao, Yong Zou, Geng Huang, Gary Wong, Chong Wang, Shihua He, Hualei Wang, Xuexing Zheng, Ying Zheng, Yongkun Zhao, Quanshui Fan, and Na Feng
- Subjects
0301 basic medicine ,medicine.drug_class ,Guinea Pigs ,030106 microbiology ,Antibodies, Viral ,medicine.disease_cause ,Monoclonal antibody ,Article ,Mice ,03 medical and health sciences ,Neutralization Tests ,medicine ,Animals ,Immunologic Factors ,Horses ,Immunoglobulin Fragments ,Ebolavirus ,Antiserum ,Mice, Inbred BALB C ,Multidisciplinary ,Ebola virus ,biology ,business.industry ,Hemorrhagic Fever, Ebola ,medicine.disease ,Survival Analysis ,Virology ,In vitro ,Disease Models, Animal ,Treatment Outcome ,030104 developmental biology ,Serum sickness ,biology.protein ,Antibody ,Post-Exposure Prophylaxis ,business - Abstract
Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.
- Published
- 2016
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