Lassa virus (LASV), which causes considerable morbidity and mortality annually, has a high genetic diversity across West Africa. LASV glycoprotein (GP) expresses this diversity, but most LASV vaccine candidates utilize only the Lineage IV LASV Josiah strain GP antigen as an immunogen and homologous challenge with Lineage IV LASV. In addition to the sequence variation amongst the LASV lineages, these lineages are also distinguished in their presentations. Inter-lineage variations within previously mapped B-cell and T-cell LASV GP epitopes and the breadth of protection in LASV vaccine/challenge studies were examined critically. Multiple alignments of the GP primary sequence of strains from each LASV lineage showed that LASV GP has diverging degrees of amino acid conservation within known epitopes among LASV lineages. Conformational B-cell epitopes spanning different sites in GP subunits were less impacted by LASV diversity. LASV GP diversity should influence the approach used for LASV vaccine design. Expression of LASV GP on viral vectors, especially in its prefusion configuration, has shown potential for protective LASV vaccines that can overcome LASV diversity. Advanced vaccine candidates should demonstrate efficacy against all LASV lineages for evidence of a pan-LASV vaccine.

中文翻译：

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Lassa病毒糖蛋白表位的谱系间变异：对Lassa病毒疫苗开发的挑战。

拉萨病毒（LASV）每年导致相当高的发病率和死亡率，在整个西非地区具有很高的遗传多样性。LASV糖蛋白（GP）表现出这种多样性，但大多数LASV候选疫苗仅利用Lineage IV LASV Josiah株GP抗原作为免疫原和与Lineage IV LASV的同源性攻击。除了LASV谱系之间的序列变异外，这些谱系在它们的表现形式中也很出色。严格检查了先前绘制的B细胞和T细胞LASV GP表位之间的谱系间差异以及LASV疫苗/挑战研究中的保护范围。来自每个LASV谱系的菌株GP一级序列的多重比对显示，LASV GP在LASV谱系中已知表位内具有不同程度的氨基酸保守性。跨GP亚基不同位点的构象B细胞表位受LASV多样性的影响较小。LASV GP的多样性应影响LASV疫苗设计所使用的方法。LASV GP在病毒载体上的表达，特别是在其融合前配置中，已显示出可以克服LASV多样性的保护性LASV疫苗的潜力。候选高级疫苗应显示出对所有LASV谱系的效力，以作为泛LAV疫苗的证据。