Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.

拉萨病毒每年在西非农村地区感染成千上万人，导致大量拉萨热（LF）病例，这是一种与高发病率和高死亡率相关的发热性疾病。缺乏批准的治疗或干预措施突显了对有效疫苗的需求。至少有四个病毒谱系在整个西非的特定区域中流通，具有重要的谱系核苷酸和氨基酸多样性。应该设计一种有效的疫苗，以引起所有谱系的拉萨病毒特异性体液免疫和细胞介导的免疫。当前大多数候选疫苗仅使用由在塞拉利昂，利比里亚和几内亚附近传播的拉萨病毒编码的IV族抗原，而不使用发现I-III族的尼日利亚。由于已知先前的感染可以预防疾病免遭随后的感染，因此我们试图确定来自尼日利亚和塞拉利昂的LF幸存者是否携带对谱系IV抗原有反应的记忆T细胞。我们的结果表明，来自尼日利亚LF幸存者的CD8 + T细胞与谱系IV抗原具有高度的交叉反应性。此外，我们确定了Lassa病毒糖蛋白复合物和核蛋白中有助于这些反应的区域，而在我们的研究组中，T细胞表位并未得到广泛保守。这些数据对于当前努力设计有效和高效的候选疫苗非常重要，这些候选疫苗可以引发所有Lassa病毒谱系的保护性免疫。我们的结果表明，来自尼日利亚LF幸存者的CD8 + T细胞与谱系IV抗原具有高度的交叉反应性。此外，我们确定了Lassa病毒糖蛋白复合物和核蛋白中有助于这些反应的区域，而在我们的研究组中，T细胞表位并未得到广泛保守。这些数据对于当前努力设计有效和高效的候选疫苗非常重要，这些候选疫苗可以引发所有Lassa病毒谱系的保护性免疫。我们的结果表明，来自尼日利亚LF幸存者的CD8 + T细胞与谱系IV抗原具有高度的交叉反应性。此外，我们确定了Lassa病毒糖蛋白复合物和核蛋白中有助于这些反应的区域，而在我们的研究组中T细胞表位并未得到广泛保守。这些数据对于当前设计有效且高效的候选疫苗可以引起所有Lassa病毒谱系的保护性免疫至关重要。