Monoclonal antibody therapy for junin virus infection

Larry Zeitlin, Joan B. Geisbert, Daniel J. Deer, Karla A. Fenton, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Do Kim, Andrew Hiatt, Michael H. Pauly, Jesus Velasco, Kevin J. Whaley, Friedrich Altmann, Clemens Gruber, Herta Steinkellner, Anna N. Honko, Ana I. Kuehne, M. Javad Aman, Sara Sahandi, Sven EnterleinXiaoguo Zhan, Delia Enria, Thomas W. Geisbert

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4458-4463
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number16
DOIs
StatePublished - Apr 19 2016

Keywords

  • Hemorrhagic fever
  • Immunotherapy
  • Junin
  • Therapy

ASJC Scopus subject areas

  • General

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    Zeitlin, L., Geisbert, J. B., Deer, D. J., Fenton, K. A., Bohorov, O., Bohorova, N., Goodman, C., Kim, D., Hiatt, A., Pauly, M. H., Velasco, J., Whaley, K. J., Altmann, F., Gruber, C., Steinkellner, H., Honko, A. N., Kuehne, A. I., Aman, M. J., Sahandi, S., ... Geisbert, T. W. (2016). Monoclonal antibody therapy for junin virus infection. Proceedings of the National Academy of Sciences of the United States of America, 113(16), 4458-4463. https://doi.org/10.1073/pnas.1600996113