Monoclonal antibody therapy protects nonhuman primates against mucosal exposure to Lassa virus

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

Research output: Contribution to journalArticlepeer-review

Abstract

Lassa fever (LF) is an acute viral illness that causes thousands of deaths annually in West Africa. There are currently no Lassa virus (LASV) vaccines or antivirals approved for human use. Recently, we showed that combinations of broadly neutralizing human monoclonal antibodies (BNhuMAbs) known as Arevirumab-2 or Arevirumab-3 protected up to 100% of cynomolgus macaques against challenge with diverse lineages of LASV when treatment was initiated at advanced stages of disease. This previous work assessed efficacy against parenteral exposure. However, transmission of LASV to humans occurs primarily by mucosal exposure to virus shed from Mastomys rodents. Here, we describe the development of a lethal intranasal exposure macaque model of LF. This model is employed to show that Arevirumab cocktails rescue 100% of macaques from lethal LASV infection when treatment is initiated 8 days after LASV exposure. Our work demonstrates BNhuMAbs have utility in treating LASV infection acquired through mucosal exposure.

Original languageEnglish (US)
Article number101392
JournalCell Reports Medicine
Volume5
Issue number2
DOIs
StatePublished - Feb 20 2024

Keywords

  • Arenavirus
  • Lassa virus
  • animal model
  • antibody
  • hemorrhagic fever
  • intranasal
  • monoclonal
  • mucosal
  • neutralizing
  • nonhuman primate

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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