A human monoclonal antibody combination rescues nonhuman primates from advanced disease caused by the major lineages of Lassa virus

Robert W. Cross, Megan L. Heinrich, Karla A. Fenton, Viktoriya Borisevich, Krystle N. Agans, Abhishek N. Prasad, Courtney Woolsey, Daniel J. Deer, Natalie S. Dobias, Megan M. Rowland, Raju Lathigra, Rodrigo Borrega, Joan B. Geisbert, Robert F. Garry, Luis M. Branco, Thomas W. Geisbert

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

There are no approved treatments for Lassa fever (LF), which is responsible for thousands of deaths each year in West Africa. A major challenge in developing effective medical countermeasures against LF is the high diversity of circulating Lassa virus (LASV) strains with four recognized lineages and four proposed lineages. The recent resurgence of LASV in Nigeria caused by genetically distinct strains underscores this concern. Two LASV lineages (II and III) are dominant in Nigeria. Here, we show that combinations of two or three pan-lineage neutralizing human monoclonal antibodies (8.9F, 12.1F, 37.D) known as Arevirumab-2 or Arevirumab-3 can protect up to 100% of cynomolgus macaques against challenge with both lineage II and III LASV isolates when treatment is initiated at advanced stages of disease on day 8 after LASV exposure. This work demonstrates that it may be possible to develop postexposure interventions that can broadly protect against most strains of LASV.

Original languageEnglish (US)
Article numbere2304876120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number34
DOIs
StatePublished - Aug 22 2023

Keywords

  • antibody
  • arenavirus
  • lassa virus
  • primate
  • treatment

ASJC Scopus subject areas

  • General

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