| Author |
Honko, Anna N. Aman, M. Javad Whaley, Kevin J. Kuehne, Ana I. Steinkellner, Herta Zhan, Xiaoguo Fenton, Karla A. Bohorova, Natasha Gruber, Clemens Geisbert, Joan B. Hiatt, Andrew Goodman, Charles Deer, Daniel J. Pauly, Michael H. Sahandi, Sara Velasco, Jesus Zeitlin, Larry Geisbert, Thomas W. Enterlein, Sven Enria, Delia Bohorov, Ognian Kim, Do Altmann, Friedrich |
| Description |
Author Affiliation: Zeitlin L ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Geisbert JB ( Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555); Deer DJ ( Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555); Fenton KA ( Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555); Bohorov O ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Bohorova N ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Goodman C ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Kim D ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Hiatt A ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Pauly MH ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Velasco J ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Whaley KJ ( Mapp Biopharmaceutical, Inc., San Diego, CA 92121); Altmann F ( Department of Chemistry, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria); Gruber C ( Department of Chemistry, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria); Steinkellner H ( Department of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria); Honko AN ( Virology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702); Kuehne AI ( Virology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702); Aman MJ ( Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878); Sahandi S ( Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878); Enterlein S ( Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878); Zhan X ( Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878); Enria D ( Instituto Nacional de Enfermedades Virales Humanas, Buenos Aires, Argentina.); Geisbert TW ( Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555); |
| 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. |
