Immunogenicity and protective potential of a Plasmodium spp. enolase peptide displayed on archaeal gas vesicle nanoparticles
Immunogenicity and protective potential of a Plasmodium spp. enolase peptide displayed on archaeal gas vesicle nanoparticles
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DOI：
10.1186/s12936-015-0914-x
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发表时间：
2015-10-14
期刊：
影响因子：
3
通讯作者：
Jarori, Gotam K.
中科院分区：
文献类型：
--
作者：
Dutta, Sneha;DasSarma, Priya;Jarori, Gotam K.
背景：恶性疟原虫烯醇化酶定位于裂殖子和卵母细胞表面。重组疟原虫烯醇化酶(RPfeno)免疫小鼠对疟疾有部分保护作用。抗rPfeno抗体可抑制体外培养的蚊虫生长，并阻断蚊虫中肠上皮细胞的运动侵袭。推测寄生虫特异的兼职功能(如宿主细胞入侵)可能映射到Pfeno的独特结构元件上。由于烯醇化酶在寄主和寄生虫之间高度保守，因此在嗜盐古盐生杆菌产生的新型蛋白纳米颗粒上显示了寄生虫特异性的烯醇化酶表位。方法：利用基因工程技术，将具有保护性抗原性的疟原虫烯醇化酶特异性多肽序列(104)EWGWS(108)插入免疫原性气泡纳米颗粒(GVNPs)表面的嗜盐杆菌气泡蛋白GvpC中。分别用野生型(WT)和含有重组GVNPs(Rec)的插入物免疫两组小鼠。第三组小鼠作为未免疫对照。用酶联免疫吸附试验检测3种抗原(Wt-GVNPs、Rec-GVNPs和rPfeno)的抗体滴度。结果：rPfeno和Rec-GVNPs免疫小鼠产生了较高的抗体滴度，表明免疫小鼠产生了针对寄生虫烯醇化酶特异性插入序列的抗体。用致死品系的小鼠疟原虫攻击未免疫的WT-GVNP和Rec-GVNP免疫的小鼠，与对照组相比，Rc-GVNP免疫组的寄生虫血症显著降低，存活时间延长。Rec-GVNP-组的生存优势程度与抗rPfeno抗体滴度呈正相关，与寄生虫血症呈负相关。这些结果表明，展示在嗜盐杆菌GVNPs上的寄生虫烯醇化酶序列是一种很好的保护性抗原表位。结论：本工作表明该寄生虫特异性多肽序列是一种保护性抗原表位。虽然B细胞对Rec-GVNPs中客体序列的抗体反应轻微，但在控制寄生虫血症和生存方面有明显的优势。未来需要努力展示具有保护性的多个抗原，以提高基于GVNP的方法的性能。
Background: Plasmodium falciparum enolase has been shown to localize on the surface of merozoites and ookinetes. Immunization of mice with recombinant Plasmodium enolase (rPfeno) showed partial protection against malaria. Anti-rPfeno antibodies inhibited growth of the parasite in in vitro cultures and blocked ookinete invasion of mosquito midgut epithelium. It is hypothesized that parasite specific moonlighting functions (e.g. host cell invasion) may map on to unique structural elements of Pfeno. Since enolases are highly conserved between the host and the parasite, a parasite-specific epitope of enolase was displayed on novel protein nanoparticles produced by a halophilic Archaeon Halobacterium sp. NRC-1 and tested their ability to protect mice against live challenge.Methods: By genetic engineering, a Plasmodium-enolase specific peptide sequence (104)EWGWS(108) with protective antigenic potential was inserted into the Halobacterium gas vesicle protein GvpC, a protein localized on the surface of immunogenic gas vesicle nanoparticles (GVNPs). Two groups of mice were immunized with the wild type (WT) and the insert containing recombinant (Rec) GVNPs respectively. A third group of mice was kept as un-immunized control. Antibody titres were measured against three antigens (i.e. WT-GVNPs, Rec-GVNPs and rPfeno) using ELISA. The protective potential was determined by measuring percentage parasitaemia and survival after challenge with the lethal strain Plasmodium yoelii 17XL.Results: Rec-GVNP-immunized mice showed higher antibody titres against rPfeno and Rec-GVNPs, indicating that the immunized mice had produced antibodies against the parasite enolase-specific insert sequence. Challenging the un-immunized, WT-GVNP and Rec-GVNP-immunized mice with a lethal strain of mice malarial parasite showed significantly lower parasitaemia and longer survival in the Rec-GVNP-immunized group as compared to control groups. The extent of survival advantage in the Rec-GVNP-group showed positive correlation with anti-rPfeno antibody titres while the parasitaemia showed a negative correlation. These results indicate that the parasite enolase peptide insert displayed on Halobacterium GVNPs is a good candidate as a protective antigenic epitope.Conclusion: The work reported here showed that the parasite-specific peptide sequence is a protective antigenic epitope. Although antibody response of B-cells to the guest sequence in Rec-GVNPs was mild, significant advantage in the control of parasitaemia and survival was observed. Future efforts are needed to display multiple antigens with protective properties to improve the performance of the GVNP-based approach.