Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

Xuexing Zheng, Gary Wong, Yongkun Zhao, Hualei Wang, Shihua He, Yuhai Bi, Weijin Chen, Hongli Jin, Weiwei Gai, Di Chu, Zengguo Cao, Chong Wang, Quanshui Fan, Hang Chi, Yuwei Gao, Tiecheng Wang, Na Feng, Feihu Yan, Geng Huang, Ying ZhengNan Li, Yuetao Li, Jun Qian, Yong Zou, Gary Kobinger, George Fu Gao, Xiangguo Qiu, Songtao Yang, Xianzhu Xia

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Recent successes with monoclonal antibody cocktails ZMapp TM 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.

Original languageEnglish (US)
Article number24179
JournalScientific reports
Volume6
DOIs
StatePublished - Apr 12 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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