BACKGROUND The circumsporozoite protein (CSP) of Plasmodium is a key surface antigen that induces antibodies and T-cells, conferring immune protection in animal models and humans. However, much of the work on CSP and immunity has been developed based on studies using rodent or non-human primate CSP antigens, which may not be entirely translatable to CSP expressed by human malaria parasites, especially considering the host specificity of the different species. METHODS Using a genetically engineered strain of Plasmodium berghei that expresses luciferase, GFP and the Plasmodium falciparum orthologue of CSP, the effect of laboratory preparation, mosquito treatment and mouse factors on sporozoite infectivity was assessed using an in vivo bioluminescence assay on mice. This assay was compared with a PCR-based protection assay using an already described monoclonal antibody that can provide sterile protection against sporozoite challenge. RESULTS Bioluminescence assay demonstrated similar detection levels of the quantity and kinetics of liver-stage infection, compared to PCR-based detection. This assay was used to evaluate treatment of sporozoite and delivery method on mouse infectivity, as well as the effects of age, sex and strain of mice. Finally, this assay was used to test the protective capacity of monoclonal antibody AB317; results strongly recapitulate the findings of previous work on this antibody. CONCLUSIONS The PbGFP-Luc line and in vivo bioluminescence imaging provide highly sensitive read-outs of liver-stage infection in mice, and this method can be useful to reliably evaluate potency of pre-erythrocytic interventions.

中文翻译：

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优化体内模型以研究对恶性疟原虫红细胞前阶段的免疫力。

背景技术疟原虫的子孢子体蛋白（CSP）是一种关键的表面抗原，可诱导抗体和T细胞，在动物模型和人类中提供免疫保护。但是，有关CSP和免疫的许多工作是基于使用啮齿动物或非人灵长类CSP抗原的研究而开发的，特别是考虑到不同物种的宿主特异性，这些抗原可能无法完全转化为人类疟疾寄生虫表达的CSP。方法使用表达荧光素酶，GFP和CSP恶性疟原虫直系同源基因的伯氏疟原虫基因工程菌株，通过体内生物发光试验对小鼠的实验室准备，蚊子处理和小鼠因素对子孢子感染性的影响进行了评估。使用已经描述的单克隆抗体，将这种测定法与基于PCR的保护测定法进行比较，该单克隆抗体可以提供针对子孢子激发的无菌保护。结果与基于PCR的检测相比，生物发光测定显示出肝阶段感染数量和动力学的相似检测水平。该试验用于评价子孢子的治疗和递送方法对小鼠的感染性，以及小鼠的年龄，性别和品系的影响。最后，该测定法用于测试单克隆抗体AB317的保护能力。结果强烈概括了该抗体先前的研究结果。结论PbGFP-Luc细胞系和体内生物发光成像可为小鼠肝阶段感染提供高度灵敏的读数，