Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555.
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2304876120. doi: 10.1073/pnas.2304876120. Epub 2023 Aug 17.
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.
目前尚无拉沙热 (LF) 的获批疗法，该病每年在西非导致数千人死亡。开发针对 LF 的有效医疗对策的主要挑战是，循环拉沙病毒 (LASV) 株具有高度多样性，有四个公认的谱系和四个提议的谱系。最近在尼日利亚由遗传上不同的毒株引起的 LASV 再现突出了这一担忧。两种 LASV 谱系 (II 和 III) 在尼日利亚占主导地位。在这里，我们表明，被称为 Arevirumab-2 或 Arevirumab-3 的两种或三种泛谱系中和人单克隆抗体 (8.9F、12.1F、37.D) 的组合可在 LASV 暴露后第 8 天疾病进展阶段开始治疗时，针对谱系 II 和 III LASV 分离株，为高达 100%的食蟹猴提供保护。这项工作表明，有可能开发出可广泛针对大多数 LASV 株的暴露后干预措施。
