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伯氏疟原虫子孢子和环子孢子蛋白疫苗免疫的免疫反应基因调控。用全生物体疫苗和亚单位疫苗克服遗传限制。

Immune response gene regulation of immunity to Plasmodium berghei sporozoites and circumsporozoite protein vaccines. Overcoming genetic restriction with whole organism and subunit vaccines.

作者信息

Hoffman S L, Berzofsky J A, Isenbarger D, Zeltser E, Majarian W R, Gross M, Ballou W R

机构信息

Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20814-5055.

出版信息

J Immunol. 1989 May 15;142(10):3581-4.

PMID:2497175
Abstract

We conducted a series of experiments to define Ir gene regulation of the immune response to Plasmodium berghei sporozoites and circumsporozoite (CS) protein-derived subunit vaccines. The studies demonstrated that there is no apparent genetic restriction of the capacity to develop protective immunity against a large sporozoite challenge after immunization with irradiation-attenuated P. berghei sporozoites; that the Th response to (Asp-Pro-Ala-Pro-Pro-Asn-Ala-Asn)n, the predominant protective B epitope on the P. berghei CS protein, is genetically restricted and regulated by Class II genes (I-Ab) and by genes in the Class I region (H-2Dk) or telomeric to this region; and that this restriction can be overcome by immunization with a r protein including the entire P. berghei CS protein. The results support the development of full length human CS protein vaccines to take advantage of all potential T epitopes on this protein.

摘要

我们进行了一系列实验,以确定免疫反应相关基因(Ir基因)对伯氏疟原虫子孢子和环子孢子(CS)蛋白衍生亚单位疫苗的调控作用。研究表明,在用辐照减毒的伯氏疟原虫子孢子免疫后,针对大量子孢子攻击产生保护性免疫的能力没有明显的遗传限制;对伯氏疟原虫CS蛋白上主要的保护性B表位(Asp-Pro-Ala-Pro-Pro-Asn-Ala-Asn)n的Th反应受到遗传限制,并由II类基因(I-Ab)以及I类区域(H-2Dk)或该区域端粒处的基因调控;并且这种限制可以通过用包含完整伯氏疟原虫CS蛋白的重组蛋白免疫来克服。这些结果支持开发全长人CS蛋白疫苗,以利用该蛋白上所有潜在的T表位。

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引用本文的文献

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Why functional pre-erythrocytic and bloodstage malaria vaccines fail: a meta-analysis of fully protective immunizations and novel immunological model.为什么功能性原虫前期和红内期疟疾疫苗会失败:完全保护免疫接种和新型免疫模型的荟萃分析。
PLoS One. 2010 May 19;5(5):e10685. doi: 10.1371/journal.pone.0010685.
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Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity.缺乏嘌呤核苷磷酸化酶的减毒约氏疟原虫可提供保护性免疫。
Nat Med. 2008 Sep;14(9):954-8. doi: 10.1038/nm.1867.
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Dominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys.
恶性疟原虫裂殖子表面蛋白MSP1保守B细胞表位在初免普通狨猴血液期感染中的优势地位
Infect Immun. 1996 May;64(5):1502-9. doi: 10.1128/iai.64.5.1502-1509.1996.
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Cultivation of the exoerythrocytic stage of Plasmodium berghei in primary cultures of mouse hepatocytes and continuous mouse cell lines.伯氏疟原虫红细胞外期在小鼠肝细胞原代培养物和连续小鼠细胞系中的培养。
In Vitro Cell Dev Biol. 1989 Sep;25(9):857-62. doi: 10.1007/BF02623670.
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T lymphocytes from mice immunized with irradiated sporozoites eliminate malaria from hepatocytes.用经辐射的子孢子免疫的小鼠的T淋巴细胞可清除肝细胞中的疟疾。
Bull World Health Organ. 1990;68 Suppl(Suppl):132-7.
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A malaria sporozoite surface antigen distinct from the circumsporozoite protein.一种不同于环子孢子蛋白的疟原虫孢子体表面抗原。
Bull World Health Organ. 1990;68 Suppl(Suppl):152-7.
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Genetic restriction of protective immunity to Plasmodium yoelii sporozoites.对约氏疟原虫子孢子保护性免疫的遗传限制。
Bull World Health Organ. 1990;68 Suppl(Suppl):104-8.
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The circumsporozoite protein of Plasmodium: a mechanism of immune evasion by the malaria parasite?疟原虫的环子孢子蛋白:疟原虫的一种免疫逃避机制?
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Active and passive immunization against Plasmodium yoelii sporozoites.针对约氏疟原虫子孢子的主动免疫和被动免疫。
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Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.细胞毒性T细胞识别疟原虫感染的肝细胞上环子孢子蛋白的一种肽段。
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