Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques.
Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (Nicotiana benthamiana) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (P < 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.
Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA. olinger@us.army.mil
Gene Garrard
GG
Olinger
James
J
Pettitt
Do
D
Kim
Cara
C
Working
Ognian
O
Bohorov
Barry
B
Bratcher
Ernie
E
Hiatt
Steven D
SD
Hume
Ashley K
AK
Johnson
Josh
J
Morton
Michael
M
Pauly
Kevin J
KJ
Whaley
Calli M
CM
Lear
Julia E
JE
Biggins
Corinne
C
Scully
Lisa
L
Hensley
Larry
L
Zeitlin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000627:therapeutic use*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D008253:Macaca mulatta; D046549:Plantibodies / Q000302:isolation & purification / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D046549:Plantibodies