Zalgen Labs, LCC, Germantown, MD, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Sci Rep. 2020 Sep 29;10(1):16030. doi: 10.1038/s41598-020-72539-w.
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.
拉萨病毒（LASV）是拉萨热的病原体，拉萨热是一种常见的致命性出血性疾病，在西非流行。已鉴定出七种遗传上不同的 LASV 谱系。作为 CEPI（传染病防范创新联盟）拉沙疫苗开发计划的一部分，我们评估了人类免疫系统针对来自最常见的 LASV 谱系（尼日利亚的谱系 II 和 III 以及塞拉利昂的谱系 IV）的抗原产生交叉反应和交叉保护体液免疫反应的潜力。来自尼日利亚或塞拉利昂拉萨热幸存者血液中的 IgG 和 IgM 对 LASV 核蛋白和两种工程化（连接和预融合）的谱系 II-IV GP 的结合表现出显著的交叉反应性。锌蛋白的交叉反应性较小。来自尼日利亚拉萨热幸存者的血清或血浆对表达谱系 II GP 的 LASV 假病毒的中和作用优于对表达谱系 III 或 IV GP 的假病毒的中和作用。塞拉利昂幸存者没有表现出线系偏好。使用 LASV 假病毒测定法确定的中和效价与使用感染性 LASV 进行蚀斑减少测定法确定的效价具有显著相关性。这些研究为比较自然感染或免疫接种后不同谱系的 LASV 体液免疫提供了指导。
