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

Jennifer M. Brannan, Shihua He, Katie A. Howell, Laura I. Prugar, Wenjun Zhu, Hong Vu, Sergey Shulenin, Shweta Kailasan, Henna Raina, Gary Wong, Md Niaz Rahim, Logan Banadyga, Kevin Tierney, Xuelian Zhao, Yuxing Li, Frederick W. Holtsberg, John M. Dye (), Xiangguo Qiu () and M. Javad Aman ()
Additional contact information
Jennifer M. Brannan: US Army Medical Research Institute of Infectious Diseases
Shihua He: Public Health Agency of Canada
Katie A. Howell: Integrated BioTherapeutics, Inc.
Laura I. Prugar: US Army Medical Research Institute of Infectious Diseases
Wenjun Zhu: Public Health Agency of Canada
Hong Vu: Integrated BioTherapeutics, Inc.
Sergey Shulenin: Integrated BioTherapeutics, Inc.
Shweta Kailasan: Integrated BioTherapeutics, Inc.
Henna Raina: Integrated BioTherapeutics, Inc.
Gary Wong: Public Health Agency of Canada
Md Niaz Rahim: Public Health Agency of Canada
Logan Banadyga: Public Health Agency of Canada
Kevin Tierney: Public Health Agency of Canada
Xuelian Zhao: University of Maryland School of Medicine
Yuxing Li: University of Maryland School of Medicine
Frederick W. Holtsberg: Integrated BioTherapeutics, Inc.
John M. Dye: US Army Medical Research Institute of Infectious Diseases
Xiangguo Qiu: Public Health Agency of Canada
M. Javad Aman: Integrated BioTherapeutics, Inc.

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08040-w

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