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Nat Commun. 2019 Jan 10;10(1):105. doi: 10.1038/s41467-018-08040-w.

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

Author information

1
US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD, 21702, USA.
2
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2, Canada.
3
Integrated BioTherapeutics, Inc., 4 Research Court, Suite 300, Rockville, MD, 20850, USA.
4
Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada.
5
Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD, 21201, USA.
6
Institute for Bioscience and Biotechnology Research, University of Maryland, 9600 Gudelsky Drive, Rockville, MD, 20850, USA.
7
US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD, 21702, USA. john.m.dye1.civ@mail.mil.
8
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB, R3E 3R2, Canada. xiangguo.qiu@canada.ca.
9
Department of Medical Microbiology, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada. xiangguo.qiu@canada.ca.
10
Integrated BioTherapeutics, Inc., 4 Research Court, Suite 300, Rockville, MD, 20850, USA. javad@integratedbiotherapeutics.com.

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.

PMID:
30631063
PMCID:
PMC6328579
DOI:
10.1038/s41467-018-08040-w
[Indexed for MEDLINE]
Free PMC Article

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