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Proc Natl Acad Sci USA. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques
[Source: Proceedings of the National Academy of the Sciences of the United States of America, full text: (LINK). Abstract, edited.]
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Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques
Gene Garrard Olinger, Jr.<SUP>a</SUP>,<SUP>1</SUP>,<SUP>2</SUP>, James Pettitt<SUP>a</SUP>,<SUP>1</SUP>, Do Kim<SUP>b</SUP>, Cara Working<SUP>c</SUP>, Ognian Bohorov<SUP>b</SUP>, Barry Bratcher<SUP>c</SUP>, Ernie Hiatt<SUP>c</SUP>, Steven D. Hume<SUP>c</SUP>, Ashley K. Johnson<SUP>c</SUP>, Josh Morton<SUP>c</SUP>, Michael Pauly<SUP>b</SUP>, Kevin J. Whaley<SUP>b</SUP>, Calli M. Lear<SUP>a</SUP>, Julia E. Biggins<SUP>a</SUP>, Corinne Scully<SUP>a</SUP>, Lisa Hensley<SUP>a</SUP>,<SUP>3</SUP>, and Larry Zeitlin<SUP>b</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; <SUP>b</SUP>Mapp Biopharmaceutical, Inc., San Diego, CA 92121; and <SUP>c</SUP>Kentucky BioProcessing, LLC, Owensboro, KY 42301
Edited by Charles J. Arntzen, Arizona State University, Tempe, AZ, and approved September 14, 2012 (received for review August 7, 2012)
Abstract
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.
Footnotes
<SUP>1</SUP>G.G.O. and J.D.P contributed equally to this work.
<SUP>2</SUP>To whom correspondence may be addressed. E-mail: larry.zeitlin@mappbio.com or gene.olinger@us.army.mil.
<SUP>3</SUP>Present address: Office of the Chief Scientist, US Food and Drug Administration, Medical Science Countermeasures Initiative, Silver Spring, MD 20993.
Author contributions: G.G.O., B.B., E.H., S.D.H., A.K.J., J.M., M.P., K.J.W., C.M.L., J.E.B., C.S., L.H., and L.Z. designed research; J.P., D.K., C.W., O.B., E.H., S.D.H., A.K.J., J.M., M.P., and L.Z. performed research; G.G.O., J.P., O.B., B.B., E.H., S.D.H., A.K.J., J.M., M.P., C.M.L., J.E.B., C.S., L.H., and L.Z. analyzed data; and G.G.O., J.P., D.K., C.W., O.B., B.B., E.H., S.D.H., A.K.J., J.M., M.P., K.J.W., C.M.L., J.E.B., C.S., L.H., and L.Z. wrote the paper.
Conflict of interest statement: K.J.W. and L.Z. are owners of Mapp Biopharmaceutical, Inc.
This article is a PNAS Direct Submission.
Freely available online through the PNAS open access option.
-<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Division of Virology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702; <SUP>b</SUP>Mapp Biopharmaceutical, Inc., San Diego, CA 92121; and <SUP>c</SUP>Kentucky BioProcessing, LLC, Owensboro, KY 42301
Edited by Charles J. Arntzen, Arizona State University, Tempe, AZ, and approved September 14, 2012 (received for review August 7, 2012)
Abstract
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.
- passive immunization
- therapy
Footnotes
<SUP>1</SUP>G.G.O. and J.D.P contributed equally to this work.
<SUP>2</SUP>To whom correspondence may be addressed. E-mail: larry.zeitlin@mappbio.com or gene.olinger@us.army.mil.
<SUP>3</SUP>Present address: Office of the Chief Scientist, US Food and Drug Administration, Medical Science Countermeasures Initiative, Silver Spring, MD 20993.
Author contributions: G.G.O., B.B., E.H., S.D.H., A.K.J., J.M., M.P., K.J.W., C.M.L., J.E.B., C.S., L.H., and L.Z. designed research; J.P., D.K., C.W., O.B., E.H., S.D.H., A.K.J., J.M., M.P., and L.Z. performed research; G.G.O., J.P., O.B., B.B., E.H., S.D.H., A.K.J., J.M., M.P., C.M.L., J.E.B., C.S., L.H., and L.Z. analyzed data; and G.G.O., J.P., D.K., C.W., O.B., B.B., E.H., S.D.H., A.K.J., J.M., M.P., K.J.W., C.M.L., J.E.B., C.S., L.H., and L.Z. wrote the paper.
Conflict of interest statement: K.J.W. and L.Z. are owners of Mapp Biopharmaceutical, Inc.
This article is a PNAS Direct Submission.
Freely available online through the PNAS open access option.
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