Giuseppe
Emeritus
[Source: Proc Natl Acad Sci USA, full text: (LINK). Abstract, edited.]
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Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease
John M. Dye<SUP>1</SUP>,<SUP>2</SUP>, Andrew S. Herbert, Ana I. Kuehne, James F. Barth, Majidat A. Muhammad, Samantha E. Zak, Ramon A. Ortiz, Laura I. Prugar, and William D. Pratt<SUP>1</SUP>
<SUP></SUP>
Author Affiliations: Division of Virology, US Army Medical Research Institute for Infectious Diseases, Frederick, MD 21702
Edited* by Charles J. Arntzen, Arizona State University, Tempe, AZ, and approved February 9, 2012 (received for review January 10, 2012)
Abstract
Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease. In the first study, Marburg virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus-specific IgG, with additional treatments on days 4 and 8 postexposure. The postexposure IgG treatment was completely protective, with no signs of disease or detectable viremia. MARV-specific IgM antibody responses were generated, and all macaques survived rechallenge with MARV, suggesting that they generated an immune response to virus replication. In the next set of studies, NHPs were infected with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with additional treatments on days 4 and 8 postexposure. The delayed treatments protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three IgG-treated NHPs had no clinical signs of illness, with the third NHP developing mild and delayed signs of disease followed by full recovery. These studies clearly demonstrate that postexposure antibody treatments can protect NHPs and open avenues for filovirus therapies for human use using established Food and Drug Administration-approved polyclonal or monoclonal antibody technologies.
passive antibody polyclonal antibody therapeutic agent hemorrhagic fever virus
Footnotes
<SUP>1</SUP>J.M.D. and W.D.P. contributed equally to this work.
<SUP>2</SUP>To whom correspondence should be addressed. E-mail: john.m.dye1@us.army.mil.
Author contributions: J.M.D., A.S.H., A.I.K., J.F.B., R.A.O., and W.D.P. designed research; J.M.D., A.S.H., A.I.K., J.F.B., M.A.M., S.E.Z., R.A.O., L.I.P., and W.D.P. performed research; J.M.D., A.S.H., A.I.K., M.A.M., S.E.Z., and W.D.P. analyzed data; and J.M.D., A.S.H., and W.D.P. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200409109/-/DCSupplemental.
-John M. Dye<SUP>1</SUP>,<SUP>2</SUP>, Andrew S. Herbert, Ana I. Kuehne, James F. Barth, Majidat A. Muhammad, Samantha E. Zak, Ramon A. Ortiz, Laura I. Prugar, and William D. Pratt<SUP>1</SUP>
<SUP></SUP>
Author Affiliations: Division of Virology, US Army Medical Research Institute for Infectious Diseases, Frederick, MD 21702
Edited* by Charles J. Arntzen, Arizona State University, Tempe, AZ, and approved February 9, 2012 (received for review January 10, 2012)
Abstract
Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease. In the first study, Marburg virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus-specific IgG, with additional treatments on days 4 and 8 postexposure. The postexposure IgG treatment was completely protective, with no signs of disease or detectable viremia. MARV-specific IgM antibody responses were generated, and all macaques survived rechallenge with MARV, suggesting that they generated an immune response to virus replication. In the next set of studies, NHPs were infected with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with additional treatments on days 4 and 8 postexposure. The delayed treatments protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three IgG-treated NHPs had no clinical signs of illness, with the third NHP developing mild and delayed signs of disease followed by full recovery. These studies clearly demonstrate that postexposure antibody treatments can protect NHPs and open avenues for filovirus therapies for human use using established Food and Drug Administration-approved polyclonal or monoclonal antibody technologies.
passive antibody polyclonal antibody therapeutic agent hemorrhagic fever virus
Footnotes
<SUP>1</SUP>J.M.D. and W.D.P. contributed equally to this work.
<SUP>2</SUP>To whom correspondence should be addressed. E-mail: john.m.dye1@us.army.mil.
Author contributions: J.M.D., A.S.H., A.I.K., J.F.B., R.A.O., and W.D.P. designed research; J.M.D., A.S.H., A.I.K., J.F.B., M.A.M., S.E.Z., R.A.O., L.I.P., and W.D.P. performed research; J.M.D., A.S.H., A.I.K., M.A.M., S.E.Z., and W.D.P. analyzed data; and J.M.D., A.S.H., and W.D.P. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200409109/-/DCSupplemental.
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