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首页> 外文期刊>Infection and immunity >Protective immune responses to apical membrane antigen 1 of Plasmodium chabaudi involve recognition of strain-specific epitopes.
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Protective immune responses to apical membrane antigen 1 of Plasmodium chabaudi involve recognition of strain-specific epitopes.

机译:对chabaudi疟原虫顶膜抗原1的保护性免疫应答涉及对菌株特异性表位的识别。

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Apical membrane antigen 1 (AMA-1), an asexual blood-stage antigen of Plasmodium falciparum, is an important candidate for testing as a component of a malaria vaccine. This study investigates the nature of diversity in the Plasmodium chabaudi adami homolog of AMA-1 and the impact of that diversity on the efficacy of the recombinant antigen as a vaccine against challenge with a heterologous strain of P. chabaudi. The nucleotide sequence of the AMA-1 gene from strain DS differs from the published 556KA sequence at 79 sites. The large number of mutations, the nonrandom distribution of both synonymous and nonsynonymous mutations, and the nature of both the codon changes and the resulting amino acid substitutions suggest that positive selection operates on the AMA-1 gene in regions coding for antigenic sites. Protective immune responses induced by AMA-1 were strain specific. Immunization of mice with the refolded ectodomain of DS AMA-1 provided partial protection against challenge with virulent DS (homologous) parasites but failed to protect against challenge with avirulent 556KA (heterologous) parasites. Passive immunization of mice with rabbit antibodies raised against the same antigen had little effect on heterologous challenge but provided significant protection against the homologous DS parasites.
机译:顶端膜抗原1(AMA-1)是恶性疟原虫的无性血液阶段抗原,是作为疟疾疫苗成分进行检测的重要候选药物。这项研究调查了AMA-1的疟原虫chabaudi adami同源物中多样性的性质,以及该多样性对重组抗原作为抗Chabaudi异源菌株攻击的疫苗的功效的影响。来自DS菌株的AMA-1基因的核苷酸序列在79个位点不同于已公开的556KA序列。大量的突变,同义和非同义突变的非随机分布以及密码子变化和所得氨基酸取代的性质表明,阳性选择在编码抗原位点的区域对AMA-1基因起作用。 AMA-1诱导的保护性免疫应答具有应变特异性。用重折叠的DS AMA-1胞外域对小鼠进行免疫可部分抵抗强毒DS(同源)寄生虫的攻击,但无法抵抗无毒556KA(异源)寄生虫的攻击。用针对相同抗原的兔抗体进行的被动免疫小鼠对异源攻击几乎没有影响,但对同源DS寄生虫提供了显着的保护。

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