Protective immune responses to apical membrane antigen 1 of Plasmodium chabaudi involve recognition of strain-specific epitopes
Protective immune responses to apical membrane antigen 1 of Plasmodium chabaudi involve recognition of strain-specific epitopes
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DOI：
10.1128/iai.64.8.3310-3317.1996
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发表时间：
1996-08-01
影响因子：
3.1
通讯作者：
Anders, RF
中科院分区：
文献类型：
--
作者：
Crewther, PE;Matthew, MLSM;Anders, RF
顶膜抗原1（AMA-1）是恶性疟原虫的无性血液阶段抗原，是用于测试作为疟疾疫苗的组分的重要候选物。本研究调查了夏氏疟原虫（Plasmodium chabaudi）adami同源物中AMA-1的多样性的性质以及该多样性对重组抗原作为针对夏氏疟原虫（Plasmodium chabaudi）的异源株的攻击的疫苗的效力的影响。DS株AMA-1基因的核苷酸序列与已发表的556 KA序列有79个位点不同。大量的突变，同义和非同义突变的非随机分布，以及密码子变化和由此产生的氨基酸取代的性质表明，积极的选择操作的AMA-1基因编码的抗原位点的区域。AMA-1诱导的保护性免疫应答具有株系特异性。用DS AMA-1的重折叠胞外域免疫小鼠提供了针对有毒DS（同源）寄生虫的攻击的部分保护，但未能保护免受无毒556 KA（异源）寄生虫的攻击。用针对相同抗原的兔抗体对小鼠进行被动免疫对异源攻击的影响很小，但对同源DS寄生虫提供了显着的保护。
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-l 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 nocleotide 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.