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首页> 外文期刊>Vaccine >Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct
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Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct

机译：新型间日疟原虫环子孢子衍生的合成疫苗构建体的抗原性和免疫原性

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Background: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells. Methods: We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR(1) R-2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice. Results: PvNR(1) R-2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both OH and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines. Conclusions: These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide
机译：背景：环子孢子（CS）蛋白是主要的疟疾子孢子表面抗原，目前被认为是候选疫苗。间质疟原虫CS（PvCS）蛋白包含一个双态的中央重复片段，两侧是保守区，该保守区包含与宿主细胞的寄生虫侵袭有关的功能域。蛋白质的氨基（N末端）侧面具有一个裂解区（I区），这对于寄生虫入侵肝细胞之前的蛋白水解加工至关重要。方法：我们已经开发了一种131 mer长的合成多肽（LSP），名为PvNR（1）R-2，该多肽包括N端侧翼和两个天然重复变异区，称为VK210和VK247。我们研究了来自不同疟疾流行地区的人类血清中对该区域的自然免疫应答及其在小鼠中的免疫原性。结果：通过ELISA检测时，来自巴布亚新几内亚（PNG）的血清（83％）比来自哥伦比亚（24％）的血清更经常识别PvNR（1）R-2。在Montanide ISA51佐剂中配制的多肽在OH和CB6F1小鼠品系中均引起强烈的抗体反应。通过IFA测试，来自免疫小鼠的抗体以及亲和纯化的人IgG与天然蛋白反应。此外，小鼠免疫血清在体外对肝癌细胞株的子孢子入侵（ISI）具有强烈的抑制作用（90％）。结论：这些结果鼓励在非人类灵长类动物中进行进一步的研究，以确认引起子孢子侵袭阻断抗体，评估细胞介导的免疫应答和该多肽的保护功效。

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