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首页> 外文期刊>Infection and immunity >Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection
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Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

机译：疟疾预暴露对控制型人类疟疾感染后抗寄生虫细胞和体液免疫反应的影响

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To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreserved Plasmodium falciparum sporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection of P. falciparum sporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexual P. falciparum lysate and another that, based on P. falciparum serology, resembled the malaria-naive Dutch cohort. Positive P. falciparum serology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparum antibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increase P. falciparum-specific in vitro recall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower in P. falciparum lysate-seropositive individuals than in seronegative individuals. In conclusion, positive P. falciparum lysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.
机译：了解先前的疟疾暴露对抗寄生虫免疫反应的影响对于制定成功的免疫策略很重要。使用冷冻保存的恶性疟原虫子孢子控制人类的疟疾感染（CHMI）提供了独特的机会来研究来自不同传播背景和遗传背景的个体在获得或召回抗疟疾免疫反应方面的差异。在这项研究中，我们比较了来自疟疾低流行地区的两个疟疾天真的荷兰志愿者和坦桑尼亚人的抗寄生虫体液和细胞免疫反应，他们通过皮内注射恶性疟原虫子孢子接受相同的CHMI方案。来自两个试验的样品在一个中心进行了平行分析，以确保免疫结果的直接可比性。在坦桑尼亚队列中，我们区分出一组具有中等水平的无性恶性疟原虫溶胞产物预先存在的抗体，而另一组基于恶性疟原虫血清学，类似于无疟疾的荷兰人群。基线时，恶性疟原虫血清学检测阳性的患者与通过CHMI进行定量PCR（qPCR）首次检测到的寄生虫密度低于坦桑尼亚血清学阴性的志愿者相比。在CHMI之后，坦桑尼亚的两个小组都显示出更强的抗P值。恶性疟原虫的抗体效价比荷兰志愿者高，表明B细胞记忆水平与血清​​学无关。与荷兰人相反，坦桑尼亚人未能增加CHMI后恶性疟原虫特异性体外召回γ-干扰素（IFN-γ）的产生，而恶性疟原虫溶胞产物中固有的IFN-γ反应较低。血清阳性的个体比血清阴性的个体。总之，恶性疟原虫裂解物血清学阳性可用于鉴定具有较好的寄生虫控制能力但循环淋巴细胞中的IFN-γ反应较弱的个体，这可能有助于在未来疟疾流行地区的CHMI试验中对志愿者进行分层。

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