Post-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates

Jennifer M Brannan,Xuelian Zhao,Hong Vu,Shihua He,Kevin Tierney,Yuxing Li,Logan Banadyga,Shweta Kailasan,Wenjun Zhu,Md Niaz Rahim,M Javad Aman,Sergey Shulenin,Henna Raina,Gary Wong,Laura I Prugar,John M Dye,Xiangguo Qiu,Frederick W Holtsberg,Katie A Howell

doi:10.1038/s41467-018-08040-w

Abstract

The 2013–2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaviruses, Sudan (SUDV) and Bundibugyo (BDBV) viruses, as well as multiple variants of Marburg virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolavirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection. This cocktail when supplemented by the anti-MARV mAb MR191 exhibited 100% efficacy in MARV-infected NHPs. These findings provide a solid foundation for clinical development of broadly protective immunotherapeutics for use in future filovirus epidemics.

Highlights

The 2013–2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics
The genus Ebolavirus consists of five species each represented by a virus type: Ebola (EBOV), Sudan (SUDV), Bundibugyo (BDBV), Reston (RESTV), and Taï Forrest (TAFV) viruses, of which the first three have caused lethality in humans[1]
We evaluated the binding of FVM04, CA45, and several other previously reported monoclonal antibodies (mAbs) toward GP of EBOV, SUDV, and BDBV at neutral and acidic pH

Summary

Introduction

The 2013–2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. FVM04 and CA45 were produced in Chinese Hamster Ovary (CHO) cells and tested for potency in a model of EBOV infection in guinea pigs in which a single dose of the antibody cocktail is administered at 3 days postinfection (dpi) with the guinea pigadapted (GPA) Ebola virus (GPA-EBOV). All surviving animals had

Results

Conclusion