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用未改变的无菌疟疾寄生虫肝期进行皮下免疫可诱导对感染性子孢子攻击的无菌保护。

Subcutaneous Immunization with Unaltered Axenic Malaria Parasite Liver Stages Induces Sterile Protection against Infectious Sporozoite Challenge.

作者信息

Kamil Mohd, Deveci Gozde, Kina Umit Y, Kappe Stefan H I, Aly Ahmed S I

机构信息

Aly Lab., Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34820, Turkey.

Department of Biotechnology, Institute of Health Sciences, Bezmialem Vakif University, Istanbul 34093, Turkey.

出版信息

Vaccines (Basel). 2022 Nov 8;10(11):1884. doi: 10.3390/vaccines10111884.

DOI:10.3390/vaccines10111884
PMID:36366392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9695791/
Abstract

Host cell-free, axenic development of liver stages (LS) of the malaria parasite has been demonstrated. Here we explored axenic liver stages as a novel live whole parasite malaria vaccine platform, which is unaltered and not prone to human-error, compared to the immunization with live-attenuated sporozoites that must be done intravenously. We show that in contrast to live sporozoites, axenic LS are not infectious to the immunized host. Subcutaneous immunizations of mice with axenic LS, developed from wild-type (WT) sporozoites or WT sporozoites expressing enhanced-GFP, conferred sterile protection against infectious sporozoite challenge. Thus, axenic liver stages of and might constitute an attractive alternative to live sporozoite immunization.

摘要

疟原虫肝期(LS)在无宿主细胞、无菌条件下的发育已得到证实。在此,我们探索将无菌肝期作为一种新型的活全寄生虫疟疾疫苗平台,与必须通过静脉注射进行的减毒活子孢子免疫相比,该平台未发生改变且不易出现人为错误。我们发现,与活子孢子不同,无菌肝期对免疫宿主无感染性。用野生型(WT)子孢子或表达增强型绿色荧光蛋白的WT子孢子发育而来的无菌肝期对小鼠进行皮下免疫,可使其获得针对感染性子孢子攻击的无菌保护。因此,疟原虫和的无菌肝期可能是活子孢子免疫的一个有吸引力的替代方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/9695791/1519a88dd22b/vaccines-10-01884-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/9695791/1519a88dd22b/vaccines-10-01884-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/9695791/1519a88dd22b/vaccines-10-01884-g001.jpg

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本文引用的文献

1
An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge.一种表达肝期输出蛋白的减毒单纯疱疹病毒1型衍生疟疾疫苗可诱导针对感染性子孢子攻击的无菌保护。
Vaccines (Basel). 2022 Feb 16;10(2):300. doi: 10.3390/vaccines10020300.
2
Malaria vaccine research & innovation: the intersection of IA2030 and zero malaria.疟疾疫苗研究与创新:IA2030与零疟疾的交汇点
NPJ Vaccines. 2020 Nov 20;5(1):109. doi: 10.1038/s41541-020-00259-3.
3
Malaria vaccines since 2000: progress, priorities, products.
2000年以来的疟疾疫苗:进展、优先事项与产品
NPJ Vaccines. 2020 Jun 9;5(1):48. doi: 10.1038/s41541-020-0196-3. eCollection 2020.
4
Plasmodium falciparum pre-erythrocytic stage vaccine development.恶性疟原虫红前期疫苗的研制。
Malar J. 2020 Feb 3;19(1):56. doi: 10.1186/s12936-020-3141-z.
5
Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Challenge in a Mouse Model.用pIL-33佐剂的合成DNA疫苗驱动肝脏定位的T细胞,并在小鼠模型中提供针对攻击的保护。
Vaccines (Basel). 2020 Jan 10;8(1):21. doi: 10.3390/vaccines8010021.
6
Prospects for Malaria Vaccines: Pre-Erythrocytic Stages, Blood Stages, and Transmission-Blocking Stages.疟疾疫苗的前景:红细胞前期、红内期和传播阻断期。
Biomed Res Int. 2019 Oct 3;2019:9751471. doi: 10.1155/2019/9751471. eCollection 2019.
7
Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages.啮齿动物疟原虫无性和有性血液阶段及蚊虫阶段的表型分析
J Vis Exp. 2019 May 30(147). doi: 10.3791/55688.
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Challenges and strategies for developing efficacious and long-lasting malaria vaccines.开发有效和持久的疟疾疫苗面临的挑战和策略。
Sci Transl Med. 2019 Jan 9;11(474). doi: 10.1126/scitranslmed.aau1458.
9
The Development of Whole Sporozoite Vaccines for Malaria.疟疾全孢子疫苗的研制。
Front Immunol. 2018 Dec 11;9:2748. doi: 10.3389/fimmu.2018.02748. eCollection 2018.
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A sporozoite-based vaccination platform against human malaria.一种基于子孢子的抗人类疟疾疫苗接种平台。
NPJ Vaccines. 2018 Aug 24;3:33. doi: 10.1038/s41541-018-0068-2. eCollection 2018.