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Curr Opin Virol. 2019 Aug 8;37:97-104. doi: 10.1016/j.coviro.2019.07.003. [Epub ahead of print]

Antibody therapy for Lassa fever.

Author information

1
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
2
La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
3
Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
4
Zalgen Labs, LLC, Germantown, MD 20876, USA.
5
Zalgen Labs, LLC, Germantown, MD 20876, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: rfgarry@tulane.edu.

Abstract

Serum from convalescent Lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. Subsequently, monoclonal antibodies (MAbs) to the Lassa virus (LASV) glycoprotein produced by memory B cells of West African patients who survived Lassa fever were identified. Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein. Human mAbs were screened for reactivity to different neutralizing epitopes, potency, and broad reactivity against multiple lineages of LASV. MAbs were downselected in a guinea pig model of Lassa fever. A cocktail of three human MAbs designated Arevirumab-3 rescued 100% of Cynomolgus macaques at advanced stages of disease more than a week post-infection. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever.

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