Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei
Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei
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DOI：
10.1371/journal.pone.0012294
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发表时间：
2010-08-19
期刊：
影响因子：
3.7
通讯作者：
Angov, Evelina
中科院分区：
文献类型：
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作者：
Bergmann-Leitner, Elke S.;Mease, Ryan M.;Angov, Evelina
背景资料：疟原虫（Plasmodium）蛋白质动合子和子孢子的细胞穿越蛋白（Cell-traversal protein for okinetes and sporozoites，CelTOS）在蚊子和脊椎动物的宿主细胞的细胞穿越中起重要作用，并且是成功的疟疾感染所必需的。CelTOS在疟原虫属物种中高度保守，表明在所有物种中具有重要的功能作用。因此，针对这种高度保守的蛋白质的免疫反应，从而可能干扰其生物学功能可能会导致保护免受感染，甚至由异源物种的Plasmodium.Methodology/主要调查结果：为了验证这一假设，我们开发了一种重组密码子协调恶性疟原虫CelTOS蛋白，可以产生高产量的大肠杆菌。coli表达系统。近交系Balb/c和远交系CD-1小鼠免疫接种不同剂量的重组蛋白佐剂与Montanide伊萨720和其特征在于使用在体外和体内analysis.Conclusions/Significance：免疫与PfCelTOS导致有效的体液和细胞免疫应答，最重要的是诱导无菌保护对异源的挑战与伯氏疟原虫子孢子在近交系和远交系小鼠的比例。抗疟疾寄生虫的CelTOS特异性抗体的生物活性可能与子孢子运动性和肝细胞感染性的损害有关。结果强调了这种抗原作为红细胞前疫苗候选者的潜力，并首次证明了疟疾疫苗在物种之间具有交叉保护性。
Background: The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium.Methodology/Principal Findings: To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses.Conclusions/Significance: Immunization with PfCelTOS resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with P. berghei sporozoites in a proportion of both inbred and outbred mice. The biological activity of CelTOS-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. The results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species.