TY - JOUR
T1 - Two-mAb cocktail protects macaques against the Makona variant of Ebola virus
AU - Qiu, Xiangguo
AU - Audet, Jonathan
AU - Lv, Ming
AU - He, Shihua
AU - Wong, Gary
AU - Wei, Haiyan
AU - Luo, Longlong
AU - Fernando, Lisa
AU - Kroeker, Andrea
AU - Bovendo, Hugues Fausther
AU - Bello, Alexander
AU - Li, Feng
AU - Ye, Pei
AU - Jacobs, Michael
AU - Ippolito, Giuseppe
AU - Saphire, Erica Ollmann
AU - Bi, Shengli
AU - Shen, Beifen
AU - Gao, George F.
AU - Zeitlin, Larry
AU - Feng, Jiannan
AU - Zhang, Boyan
AU - Kobinger, Gary P.
N1 - Funding Information:
We thank K. Tierney, G. Soule, and K. Tran from PHAC-NML (National Microbiology Laboratory) for their assistance with the animal care and technical assistance. This work was supported by PHAC, a Canadian Safety and Security Program grant to G.P.K. and X.Q., and an NIH grant to G.P.K. and E.O.S. (1U19AI109762-01). G.W. is supported by the Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research and the President''s International Fellowship Initiative from CAS. This project is partially supported by the China National Key Subject of Drug Innovation (funding no. 2015ZX09102024-005 to Beijing Mabworks) and a major program of the National Natural Science Foundation of China (grant no. 81590766 to J.F.).
PY - 2016/3/9
Y1 - 2016/3/9
N2 - The 2014-2015 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a twoantibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. The chimeric MIL77E mAb cocktail is produced in engineered Chinese hamster ovary cells and is based on mAbs c13C6 and c2G4 from ZMapp. The use of only two antibodies in MIL77E opens the door to a pan-ebolavirus cocktail.
AB - The 2014-2015 Ebola virus (EBOV) outbreak in West Africa highlighted the urgent need for specific therapeutic interventions for infected patients. The human-mouse chimeric monoclonal antibody (mAb) cocktail ZMapp, previously shown to be efficacious in EBOV (variant Kikwit) lethally infected nonhuman primates (NHPs) when administration was initiated up to 5 days, was used in some patients during the outbreak. We show that a twoantibody cocktail, MIL77E, is fully protective in NHPs when administered at 50 mg/kg 3 days after challenge with a lethal dose of EBOV variant Makona, the virus responsible for the ongoing 2014-2015 outbreak, whereas a similar formulation of ZMapp protected two of three NHPs. The chimeric MIL77E mAb cocktail is produced in engineered Chinese hamster ovary cells and is based on mAbs c13C6 and c2G4 from ZMapp. The use of only two antibodies in MIL77E opens the door to a pan-ebolavirus cocktail.
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U2 - 10.1126/scitranslmed.aad9875
DO - 10.1126/scitranslmed.aad9875
M3 - Article
C2 - 26962157
AN - SCOPUS:84960417838
SN - 1946-6234
VL - 8
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 329
M1 - 329ra33
ER -