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 therapies against LF is that there are several different genetically distinct lineages of Lassa virus. Here, we show that combinations of two or three broadly neutralizing human monoclonal antibodies known as Arevirumab-2 or Arevirumab-3 can protect up to 100% of cynomolgus monkeys against challenge with two of the major lineages of Lassa virus when treatment is initiated at advanced stages of disease on day 8 after Lassa virus exposure. This work demonstrates that it may be possible to develop postexposure interventions that can broadly protect against most of the different lineages of Lassa virus.
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.