Controlled human malaria infection (CHMI) is an established model in clinical malaria research. Upon exposure to Plasmodium falciparum parasites, malaria-naive volunteers differ in dynamics and composition of their immune profiles and subsequent capacity to generate protective immunity. CHMI volunteers are either inflammatory responders who have prominent cellular IFN-γ production primarily driven by adaptive T cells, or tempered responders who skew toward antibody-mediated humoral immunity. When exposed to consecutive CHMIs under antimalarial chemoprophylaxis, individuals who can control parasitemia after a single immunization (fast responders) are more likely to be protected against a subsequent challenge infection. Fast responders tend to be inflammatory responders who can rapidly induce long-lived IFN-γ+ T cell responses. Slow responders or even non-responders can also be protected, but via a more diverse range of responses that take a longer time to reach full protective efficacy, in part due to their tempered phenotype. The latter group can be identified at baseline before CHMI by higher expression of inhibitory ligands CTLA-4 and TIM-3 on CD4+ T cells. Delineating heterogeneity in human immune responses to P. falciparum will facilitate rational design and strategy towards effective malaria vaccines.

中文翻译：

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快速而激烈与缓慢而平稳：受控人类疟疾感染模型中疟原虫免疫反应的异质性。

受控人类疟疾感染（CHMI）是临床疟疾研究中已建立的模型。在接触恶性疟原虫寄生虫后，未患过疟疾的志愿者的免疫特征的动态和组成以及随后产生保护性免疫的能力有所不同。CHMI 志愿者要么是具有主要由适应性 T 细胞驱动的显着细胞 IFN-γ 产生的炎症反应者，要么是倾向于抗体介导的体液免疫的缓和反应者。当在抗疟化学预防下连续暴露于 CHMI 时，在单次免疫后能够控制寄生虫血症的个体（快速反应者）更有可能免受随后的攻击感染。快速反应者往往是炎症反应者，可以快速诱导长寿命的 IFN-γ+ T 细胞反应。缓慢反应者甚至无反应者也可以得到保护，但通过更多样化的反应范围，需要更长的时间才能达到完全的保护功效，部分原因是它们的缓和表型。后者可以在 CHMI 之前的基线时通过 CD4+ T 细胞上抑制性配体 CTLA-4 和 TIM-3 的较高表达来识别。描述人类对恶性疟原虫免疫反应的异质性将有助于有效疟疾疫苗的合理设计和策略。