Radiation‐attenuated sporozoites induce sterilizing immunity and remain the 'gold standard' for malaria vaccine development. Despite practical challenges in translating these whole sporozoite vaccines to large‐scale intervention programmes, they have provided an excellent platform to dissect the immune responses to malaria pre‐erythrocytic (PE) stages, comprising both sporozoites and exoerythrocytic forms. Investigations in rodent models have provided insights that led to the clinical translation of various vaccine candidates—including RTS,S/AS01, the most advanced candidate currently in a trial implementation programme in three African countries. With advances in immunology, transcriptomics and proteomics, and application of lessons from past failures, an effective, long‐lasting and wide‐scale malaria PE vaccine remains feasible. This review underscores the progress in PE vaccine development, focusing on our understanding of host‐parasite immunological crosstalk in the tissue environments of the skin and the liver. We highlight possible gaps in the current knowledge of PE immunity that can impact future malaria vaccine development efforts.

中文翻译：

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对疟疾红细胞前期阶段的免疫反应：对疫苗开发的影响

辐射减毒子孢子可诱导绝育免疫，并仍然是疟疾疫苗开发的“黄金标准”。尽管将这些全子孢子疫苗转化为大规模干预计划存在实际挑战，但它们为剖析疟疾前红细胞 (PE) 阶段的免疫反应提供了一个极好的平台，包括子孢子和红细胞外形式。对啮齿动物模型的研究提供了导致各种候选疫苗临床转化的见解，包括 RTS、S/AS01，这是目前在三个非洲国家的试验实施计划中最先进的候选疫苗。随着免疫学、转录组学和蛋白质组学的进步，以及从过去失败中吸取的教训，一种有效、持久和大规模的疟疾 PE 疫苗仍然是可行的。这篇综述强调了 PE 疫苗开发的进展，重点关注我们对皮肤和肝脏组织环境中宿主-寄生虫免疫串扰的理解。我们强调了当前关于 PE 免疫的知识可能存在的空白，这些空白可能会影响未来的疟疾疫苗开发工作。