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Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease

Author:
Dye, John M., Herbert, Andrew S., Kuehne, Ana I., Barth, James F., Muhammad, Majidat A., Zak, Samantha E., Ortiz, Ramon A., Prugar, Laura I., Pratt, William D.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.13 pp. 5034-5039
ISSN:
0027-8424
Subject:
Ebolavirus, Macaca, Marburg virus, disease control, humans, immune response, immunoglobulin G, immunoglobulin M, monoclonal antibodies, viremia, virus replication
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.
Agid:
196356