Correlative humoral and cellular immunity to genetically attenuated malaria parasites in humans

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-05-05 DOI:10.1016/j.isci.2025.112589

Emil Colstrup , Rie Nakajima , Jelte M.M. Krol , Olivia A.C. Lamers , Rafael R. de Assis , Aarti Jain , Algis Jasinskas , Eva Iliopoulou , Helena M. de Bes-Roeleveld , Blandine M.D. Franke-Fayard , Meta Roestenberg , Philip L. Felgner , Rajagopal Murugan

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Abstract

Malaria caused by Plasmodium falciparum remains one of the major infectious diseases with a high burden in Sub-Saharan Africa. In spite of the advancements made in vaccine development and implementation in endemic countries, sterile and durable protection has not been achieved. Recently, we have shown the superior protective capacity of whole sporozoites attenuated to arrest late (GA2) but not early (GA1) during the liver stage development in a controlled human malaria infection study. Here we report the breadth of antigens targeted by hitherto understudied parasite liver stage immunity and convey the coherence between humoral and cellular immunity observed in our clinical study. Our findings uncover the underlying immunogenic differences between early- and late-liver stage arresting parasites and identify key liver stage antigens for future vaccine development focused on inducing sterile immunity to malaria.

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人类对基因减毒疟原虫的相关体液和细胞免疫

由恶性疟原虫引起的疟疾仍然是撒哈拉以南非洲造成沉重负担的主要传染病之一。尽管流行国家在疫苗开发和实施方面取得了进展，但没有实现无菌和持久的保护。最近，我们在一项控制的人类疟疾感染研究中显示，在肝脏发育阶段，整个孢子体减弱到晚期（GA2）而不是早期（GA1），具有优越的保护能力。在这里，我们报告了迄今为止研究不足的寄生虫肝期免疫靶向抗原的广度，并传达了在我们的临床研究中观察到的体液免疫和细胞免疫之间的一致性。我们的发现揭示了早期和晚期肝期捕获寄生虫之间潜在的免疫原性差异，并确定了未来疫苗开发的关键肝期抗原，重点是诱导对疟疾的无菌免疫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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