Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection
Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection
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DOI：
10.3389/fmicb.2014.00686
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发表时间：
2014-12-12
影响因子：
5.2
通讯作者：
Marsh, Kevin
中科院分区：
文献类型：
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作者：
Hodgson, Susanne H.;Juma, Elizabeth;Marsh, Kevin
背景：控制人类疟疾感染（CHMI）研究是加速疫苗和药物开发的重要工具。由于CHMI试验是在受控环境中进行的，因此可以对寄生虫生长动力学（PGD）和免疫反应进行前所未有的详细评估。然而，CHMI研究尚未在疟疾流行国家常规进行或用于调查恶性疟原虫的自然获得性免疫（NAI）机制。我们使用无菌、冷冻保存的恶性疟原虫子孢子进行了一项开放标签、随机CHMI初步研究（PfSPZ挑战）以评价安全性，在肯尼亚曾低至中度接触恶性疟原虫成年人中的传染性和PGD结果：所有参与者均发生了经定量聚合酶链反应（qPCR）证实的血液阶段感染。然而，1名志愿者（110名）在注射PfSPZ激发后第21天仍无症状且血膜阴性。与其他27名志愿者（中位数11.1）相比，该志愿者的寄生虫增殖率（PMR）（1.3）降低。PMR与筛选抗结核酶联免疫吸附试验（ELISA）OD值之间存在显著相关性（p = 0.044，R = -0.384），但当志愿者110被排除在分析之外时，（p = 0.112，R = -0.313）。PfSPZ Challenge在疟疾流行人群中是安全和具有传染性的，可用于评估疟疾疫苗和药物在非洲人群中的疗效。虽然我们的研究结果受到样本量的限制，但我们的初步研究首次证明，NAI可能以可检测的方式影响CHMI后的PMR，这是一个重要的发现，应在进一步的CHMI研究中进行评估。
Background: Controlled human malaria infection (CHMI) studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD) and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI) to Plasmodium falciparum.Methods: We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272).Results: All participants developed blood-stage infection confirmed by quantitative polymerase chain reaction (qPCR). However one volunteer (110) remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR) (1.3) in comparison to the other 27 volunteers (median 11.1). A significant correlation was seen between PMR and screening anti-schizont Enzyme Linked lmmunosorbent Assays (ELISA) OD (p = 0.044, R = -0.384) but not when volunteer 110 was excluded from the analysis (p = 0.112, R = -0.313).Conclusions: PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies.