Down‐selecting circumsporozoite protein‐based malaria vaccine: a comparison of malaria sporozoite challenge model
Down‐selecting circumsporozoite protein‐based malaria vaccine: a comparison of malaria sporozoite challenge model
复制标题
基于环子孢子蛋白的疟疾疫苗的下调选择：疟疾子孢子攻击模型的比较
DOI：
10.1111/pim.12624
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发表时间：
2019
影响因子：
2.2
通讯作者：
Yoshida S.
中科院分区：
文献类型：
--
作者：
Amelia F;Iyori M;Emran TB;Yamamoto DS;Genshi K;Otsuka H;One Y;Yusuf Y;Islam A;Yoshida S.
恶性疟原虫环孢子子蛋白（PfCSP）是研制红细胞前疟疾疫苗的主要靶抗原。为了在动物模型中评估PfCSP疫苗，优先采用静脉注射孢子子的方法。然而，在临床试验中，接种疫苗的人类志愿者暴露于感染疟疾的蚊子叮咬。在这项研究中，我们根据大肠杆菌产生的全长PfCSP （PfCSP - F）及其三个截断的PfCSP在小鼠中引发免疫反应和保护两种攻击模型的能力，筛选出了它们。我们发现，接种三剂PfCSP - F可获得高抗PfCSP抗体滴度，并100%保护小鼠免受感染蚊子的叮咬。同时，三剂量截断的PfCSP在接种每个截断的PfCSP后可诱导60% - 70%的保护。腺病毒- PfCSP - F和R32LR的异源初增强免疫方案对静脉注射孢子虫具有完全的保护作用。我们的研究结果表明，PfCSP - F诱导的抗重复和抗非重复区域的抗体对受感染蚊子叮咬的完全保护是必需的，而抗重复抗体在静脉注射孢子虫的保护中起重要作用。我们的研究结果提供了一个潜在的临床应用，PfCSP - F疫苗诱导的强效抗体能够中和受感染蚊子接种的真皮孢子虫和随后血液循环中的孢子虫。
Plasmodium falciparumcircumsporozoite protein (PfCSP) is the main target antigen in development of pre‐erythrocytic malaria vaccines. To evaluate PfCSP vaccines in animal models, challenge by intravenous sporozoite injection is preferentially used. However, in clinical trials, vaccinated human volunteers are exposed to the bites of malaria‐infected mosquitoes. In this study, we down‐selectedEscherichia coli‐produced full‐length PfCSP (PfCSP‐F) and its three truncated PfCSPs based on their abilities to elicit immune response and protection in mice against two challenge models. We showed that immunization with three doses of PfCSP‐F elicited high anti‐PfCSP antibody titres and 100% protection against the bites of infected mosquitoes. Meanwhile, three‐dose truncated PfCSP induced 60%‐70% protection after immunization with each truncated PfCSP. Heterologous prime‐boost immunization regimen with adenovirus‐PfCSP‐F and R32LR greatly induced complete protection against intravenous sporozoite injection. Our results suggest that Abs to both anti‐repeat and anti‐nonrepeat regions induced by PfCSP‐F are required to confer complete protection against challenge by the bites of infected mosquitoes, whereas anti‐repeat Abs play an important role in protection against intravenous sporozoite injection. Our findings provide a potential clinical application that PfCSP‐F vaccine induces potent Abs capable of neutralizing sporozoites in the dermis inoculated by infected mosquitoes and subsequently sporozoites in the blood circulation.