title: Monoclonal antibody therapy for Junin virus infection.
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.
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121; larry.zeitlin@mappbio.com twgeisbe@UTMB.EDU.
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
authors.affiliation: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.affiliation: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deer
authors.affiliation: Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Karla A
authors.initials: KA
authors.lastname: Fenton
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Ognian
authors.initials: O
authors.lastname: Bohorov
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Natasha
authors.initials: N
authors.lastname: Bohorova
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Charles
authors.initials: C
authors.lastname: Goodman
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Do
authors.initials: D
authors.lastname: Kim
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Andrew
authors.initials: A
authors.lastname: Hiatt
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Michael H
authors.initials: MH
authors.lastname: Pauly
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Jesus
authors.initials: J
authors.lastname: Velasco
authors.affiliation: Mapp Biopharmaceutical, Inc., San Diego, CA 92121;
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Whaley
authors.affiliation: Department of Chemistry, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria;
authors.forename: Friedrich
authors.initials: F
authors.lastname: Altmann
authors.affiliation: Department of Chemistry, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria;
authors.forename: Clemens
authors.initials: C
authors.lastname: Gruber
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, 1190 Vienna, Austria;
authors.forename: Herta
authors.initials: H
authors.lastname: Steinkellner
authors.affiliation: Virology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702;
authors.forename: Anna N
authors.initials: AN
authors.lastname: Honko
authors.affiliation: Virology Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702;
authors.forename: Ana I
authors.initials: AI
authors.lastname: Kuehne
authors.affiliation: Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878;
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Aman
authors.affiliation: Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878;
authors.forename: Sara
authors.initials: S
authors.lastname: Sahandi
authors.affiliation: Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878;
authors.forename: Sven
authors.initials: S
authors.lastname: Enterlein
authors.affiliation: Integrated BioTherapeutics, Inc., Gaithersburg, MD 20878;
authors.forename: Xiaoguo
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Instituto Nacional de Enfermedades Virales Humanas, Buenos Aires, Argentina.
authors.forename: Delia
authors.initials: D
authors.lastname: Enria
authors.affiliation: Galveston 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.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006478:Hemorrhagic Fever, American / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018051:Junin virus; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins
keywords: Junin; hemorrhagic fever; immunotherapy; therapy