化学减毒疟原虫子孢子可诱导特异性免疫反应、无菌免疫及针对异源攻击的交叉保护。
Chemically attenuated Plasmodium sporozoites induce specific immune responses, sterile immunity and cross-protection against heterologous challenge.
作者信息
Purcell Lisa A, Wong Kurt A, Yanow Stephanie K, Lee Moses, Spithill Terry W, Rodriguez Ana
机构信息
McGill University, Institute of Parasitology and Centre for Host-Parasite Interactions, Sainte-Anne-de-Bellevue, QC, Canada.
出版信息
Vaccine. 2008 Sep 8;26(38):4880-4. doi: 10.1016/j.vaccine.2008.07.017. Epub 2008 Jul 29.
Abstract
Vaccination with Plasmodium sporozoites attenuated by irradiation or genetic manipulation induces a protective immune response in rodent malaria models. Recently, vaccination with chemically attenuated P. berghei sporozoites (CAS) has also been shown to elicit sterile immunity in mice. Here we show that vaccination with CAS of P. yoelii also protects against homologous infection and that a P. berghei CAS vaccine cross protects against heterologous challenge with P. yoelii sporozoites. Vaccination with P. yoelii or P. berghei CAS induced parasite-specific antibodies and IFN-gamma-producing CD8(+) T cells at levels not significantly different from radiation-attenuated sporozoites. Our findings provide an initial characterization of the immune response generated by CAS vaccination and suggest that this attenuation process could be used in the production of an effective cross-protective liver stage vaccine for malaria.
摘要
用经辐射或基因操作减毒的疟原虫子孢子进行疫苗接种，可在啮齿动物疟疾模型中诱导产生保护性免疫反应。最近，用化学减毒的伯氏疟原虫子孢子（CAS）进行疫苗接种也已证明可在小鼠中引发无菌免疫。在此我们表明，用约氏疟原虫的CAS进行疫苗接种也能预防同源感染，并且一种伯氏疟原虫CAS疫苗可交叉预防约氏疟原虫子孢子的异源攻击。用约氏疟原虫或伯氏疟原虫CAS进行疫苗接种诱导产生的寄生虫特异性抗体和产生干扰素-γ的CD8(+) T细胞水平，与辐射减毒子孢子诱导产生的水平无显著差异。我们的研究结果初步描述了CAS疫苗接种所产生的免疫反应，并表明这种减毒过程可用于生产一种有效的疟疾交叉保护性肝期疫苗。
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本文引用的文献
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Chemical attenuation of Plasmodium berghei sporozoites induces sterile immunity in mice.伯氏疟原虫子孢子的化学减毒诱导小鼠产生无菌免疫。
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Cross-protection between attenuated Plasmodium berghei and P. yoelii sporozoites.伯氏疟原虫减毒株与约氏疟原虫子孢子之间的交叉保护作用。
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Protracted sterile protection with Plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by CD8+ T cells.用约氏疟原虫红细胞前期基因减毒寄生虫疟疾疫苗进行的长期无菌保护与显著的肝期持续性无关，且由CD8 + T细胞介导。
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Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells.基因减毒的伯氏疟原虫肝期诱导无菌性长期保护，这种保护由主要组织相容性复合体I类依赖性产生干扰素-γ的CD8 + T细胞介导。
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Genetically attenuated P36p-deficient Plasmodium berghei sporozoites confer long-lasting and partial cross-species protection.基因减毒的P36p缺陷型伯氏疟原虫子孢子可提供持久且部分的跨物种保护。
Int J Parasitol. 2007 Nov;37(13):1511-9. doi: 10.1016/j.ijpara.2007.05.005. Epub 2007 May 21.
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Genetically attenuated Plasmodium berghei liver stages persist and elicit sterile protection primarily via CD8 T cells.基因减毒的伯氏疟原虫肝期持续存在，并主要通过CD8 T细胞引发无菌保护。
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Pharmacogenomic analyses of targeting the AT-rich malaria parasite genome with AT-specific alkylating drugs.使用AT特异性烷基化药物靶向富含AT的疟原虫基因组的药物基因组学分析。
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Plasmodium yoelii sporozoites with simultaneous deletion of P52 and P36 are completely attenuated and confer sterile immunity against infection.同时缺失P52和P36的约氏疟原虫子孢子完全减毒，并能赋予对感染的无菌免疫力。
Infect Immun. 2007 Aug;75(8):3758-68. doi: 10.1128/IAI.00225-07. Epub 2007 May 21.
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