Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys
Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys
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DOI：
10.1080/00034989859230
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发表时间：
1998-07-01
影响因子：
--
通讯作者：
Herrera, S
中科院分区：
文献类型：
--
作者：
Arevalo-Herrera, M;Roggero, MA;Herrera, S
来自哥伦比亚太平洋沿岸两个疟疾流行村庄的个体的血浆样本和代表间日疟原虫环子孢子蛋白(CSP)中央和侧翼不同片段的合成多肽被用于精细绘制整个CSP上的B细胞表位图。此外，对Aotus猕猴的氨基(N)区和羧基(C)区对应的长肽的免疫原性进行了评价。比较了人自然感染后和人工合成的多肽免疫后识别的表位。人类样本更多地含有针对中央区域的特定抗体。CSP的I型重复区域主要由人血清识别(来自Zacarias村的68%和来自Bajo Calima的75%)，与II型重复反应的人口明显较少(分别为20%和11%)。大多数与I型重复序列反应的血清都能识别Aotus的最小表位AGDR。虽然N端和C端的多肽在Aotus中都具有很强的免疫原性，并能诱导产生持久的抗体，但C端多肽的抗体效价高于N端的抗体。用人和猴子血浆进行竞争抑制试验，可以鉴定氨基区71-90(P8)和羧基区332-361(p24/p25)上的优势B细胞表位。针对这三个表位的自然诱导抗体在Aotus中的高流行率，相应序列可能的功能作用，以及这些表位的高免疫原性，可能对以间日疟原虫CSP为基础的疟疾疫苗的开发具有重要意义。
Plasma samples of individuals from two malaria-endemic villages on the Colombian Pacific coast and synthetic peptides representing different fragments of the central and flanking regions of the Plasmodium vivax circumsporozoite protein (CSP) were used to perform a fine mapping of the B-cell epitopes on the whole CSP. In addition, the immunogenicity of long polypeptides corresponding to the amino (N) and carboxyl (C) regions was evaluated in Aotus monkeys. The epitopes recognized after natural infection of humans and after immunization of Aotus with these synthetic peptides were compared. Human samples more frequently contained specific antibodies to the central region. The type-I repeat region of the CSP was predominantly recognized by the human sera (by 68% of those from the village of Zacarias and 75% of those from Bajo Calima), a significantly smaller population reacting with the type-II repeat (20% and 11%, respectively). Most of the sera reacting with the type-I repeat recognized the minimal epitope AGDR.Although the N- and C-terminal polypeptides were both highly immunogenic in Aotus and induced long-lasting antibodies, titres of antibodies to the C-terminal polypeptide were higher than those of antibodies to the N-terminal. Competitive inhibition assays performed using human and monkey plasma allowed the identification of dominant B-cell epitopes on sequence 71-90 (p8) from the amino region and sequence 332-361 (p24/p25) from the carboxyl region. The high prevalence of naturally induced antibodies to the three epitopes, the possible functional role of the corresponding sequences, and the high immunogenicity of these epitopes in Aotus could be of great importance in the development of a malaria vaccine based on P. vivax CSP.