CONSERVED PEPTIDE SEQUENCE OF THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN AND ANTIPEPTIDE ANTIBODIES INHIBIT PLASMODIUM-BERGHEI SPOROZOITE INVASION OF HEP-G2 CELLS AND PROTECT IMMUNIZED MICE AGAINST P-BERGHEI SPOROZOITE CHALLENGE
CONSERVED PEPTIDE SEQUENCE OF THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN AND ANTIPEPTIDE ANTIBODIES INHIBIT PLASMODIUM-BERGHEI SPOROZOITE INVASION OF HEP-G2 CELLS AND PROTECT IMMUNIZED MICE AGAINST P-BERGHEI SPOROZOITE CHALLENGE
复制标题
DOI：
10.1128/iai.63.11.4375-4381.1995
复制
发表时间：
1995-11-01
影响因子：
3.1
通讯作者：
CHAUHAN, VS
中科院分区：
文献类型：
--
作者：
CHATTERJEE, S;WERY, M;CHAUHAN, VS
疟疾子孢子注入循环后几分钟进入肝细胞。入侵过程的速度和特异性表明它是受体介导的。恶性疟原虫环子孢子（CS）蛋白的II区序列包括一个九肽（WSPCSVTCG），该九肽在所有已测序的CS蛋白中高度保守，包括伯氏疟原虫的CS蛋白。我们发现基于恶性疟原虫区域II序列的两种肽P18（EWSPCSVTCGNGIQVRIK）和P32（IEQYLKKIKNS ISTEWSPCSVTCGNGIQVRIK）在体外显著抑制伯氏疟原虫子孢子侵入Hep-G2细胞。如果在子孢子侵入之前将任一肽与Hep-G2细胞预孵育，则这种抑制增强。我们证实，区域II是肝细胞受体的子孢子配体;此外，尽管恶性疟原虫和伯氏疟原虫区域II序列之间的差异很小（66%的同源性）的九肽序列，基序序列的功能特性不受影响。由于保守的蛾代表一个关键的序列参与疟原虫子孢子侵入肝细胞，抗体区II应抑制子孢子侵入肝细胞。事实上，我们发现针对基于恶性疟原虫的肽P32产生的多克隆抗体抑制伯氏疟原虫子孢子侵入Hep-GZ细胞。此外，用P32免疫的近交系小鼠（C57 BL/6）被保护免于伯氏疟原虫子孢子的致死攻击。我们的研究结果表明，CS蛋白的保守区域II包含关键的B-和T-细胞表位，这种肽序列从人疟原虫恶性疟原虫可以筛选伯氏疟原虫啮齿动物模型，最后，该区域II可以被认为是有用的疟疾疫苗的组成部分之一。
Minutes after injection into the circulation, malaria sporozoites enter hepatocytes. The speed and specificity of the invasion process suggest that it is receptor mediated. The region II sequence of Plasmodium falciparum circumsporozoite (CS) protein includes a nonapeptide (WSPCSVTCG) which is highly conserved in all of the CS proteins sequenced to data, including the one from Plasmodium berghei. We have found that two peptides based on the P. falciparum region II sequence, P18 (EWSPCSVTCGNGIQVRIK) and P32 (IEQYLKKIKNS ISTEWSPCSVTCGNGIQVRIK), significantly inhibited P. berghei sporozoite invasion into Hep-G2 cells in vitro. This inhibition was enhanced if either peptide was preincubated with Hep-G2 cells prior to sporozoite invasion. We confirm that region II is a sporozoite ligand for the hepatocyte receptor; moreover, despite the few differences between P. falciparum and P. berghei region II sequences around the nonapeptide sequence (66% homology), the functional characteristics of the motif sequences are not affected. Since the conserved moths represent a crucial sequence involved in Plasmodium sporozoite invasion of hepatocytes, antibodies to region II should inhibit sporozoite invasion into hepatocytes. Indeed, we found that polyclonal antibodies generated to the P. falciparum-based peptide P32 inhibited P. berghei sporozoite invasion of Hep-GZ cells. Furthermore, inbred mice (C57BL/6) immunized with P32 were protected against a lethal challenge of P. berghei sporozoites. Our results suggest that the conserved region II of the CS protein contains crucial B- and T-cell epitopes, that such peptide sequences from the human malaria parasite P. falciparum can be screened in the P. berghei rodent model, and, finally, that region II can be considered useful as one of the components of a malaria vaccine.