Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4458-63. doi: 10.1073/pnas.1600996113. Epub 2016 Apr 4.

Monoclonal antibody therapy for Junin virus infection.

Author information

  • 1Mapp Biopharmaceutical, Inc., San Diego, CA 92121; larry.zeitlin@mappbio.com twgeisbe@UTMB.EDU.
  • 2Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
  • 3Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
  • 4Department of Chemistry, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria;
  • 5Department of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria;
  • 6Virology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702;
  • 7Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878;
  • 8Instituto Nacional de Enfermedades Virales Humanas, Buenos Aires, Argentina.
  • 9Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555; larry.zeitlin@mappbio.com twgeisbe@UTMB.EDU.

Abstract

Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them (J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic.

KEYWORDS:

Junin; hemorrhagic fever; immunotherapy; therapy

PMID:
27044104
PMCID:
PMC4843420
DOI:
10.1073/pnas.1600996113
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center