Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8
Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8
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DOI：
10.1128/iai.00211-12
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Burns, James M., Jr.
中科院分区：
文献类型：
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作者：
Alaro, James R.;Angov, Evelina;Burns, James M., Jr.
裂殖子表面蛋白1（MSP 1（19））的C-末端19-kDa结构域是保护性抗体的靶，但单独的免疫原性差。先前，使用约氏疟原虫鼠模型，我们将约氏疟原虫MSP 1（19）（PfMSP 1（19））与全长约氏疟原虫裂殖子表面蛋白8（MSP 8）融合。免疫后，MSP 8限制性T细胞应答有助于产生高水平和持续水平的保护性PfMSP 1（19）和PyMSP 8特异性抗体。在这里，我们评估了人类疟疾寄生虫恶性疟原虫MSP 8的疫苗潜力。与PfMSP 8不同的是，恶性疟原虫MSP 8（PfMSP 8）含有N-末端天冬酰胺和天冬氨酸（Asn/Asp）丰富的结构域，其功能未知。重组全长PfMSP 8和缺乏富含Asn/Asp结构域的截短形式PfMSP 8（Δ Asn/Asp）的比较分析表明，这两种蛋白质对T细胞和B细胞具有免疫原性。利用的所有T细胞表位定位在rPfMSP 8（Δ Asn/Asp）内。优势B细胞表位是rPfMSP 8和rPfMSP 8的构象和共同的（Δ Asn/Asp）。天然PfMSP 8表达的分析揭示PfMSP 8存在于晚期裂殖子和裂殖子的细胞内。在入侵后，发现PfMSP 8分布在环状和滋养体阶段寄生虫的表面上。与PfMSP 8在裂殖子表面上的低表达和/或瞬时表达一致，PfMSP 8特异性兔IgG不抑制恶性疟原虫血液期寄生虫的体外生长。这些研究表明，PfMSP 8作为疟疾疫苗组分的进一步开发应集中于使用PfMSP 8（Δ Asn/Asp）及其保守的免疫原性T细胞表位作为弱免疫原（包括PfMSP 1）的保护性结构域的融合伴侣（19）。
The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP1(19)) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the Plasmodium yoelii murine model, we fused P. yoelii MSP1(19) (PfMSP1(19)) with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective PfMSP1(19)- and PyMSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium falciparum. Distinct from PfMSP8, P. falciparum MSP8 (PfMSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length PfMSP8 and a truncated version devoid of the Asn/Asp-rich domain, PfMSP8(Delta Asn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within rPfMSP8(Delta Asn/Asp). The dominant B cell epitopes were conformational and common to both rPfMSP8 and rPfMSP8(Delta Asn/Asp). Analysis of native PfMSP8 expression revealed that PfMSP8 is present intracellularly in late schizonts and merozoites. Following invasion, PfMSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of PfMSP8 on the surface of merozoites, PfMSP8-specific rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage parasites. These studies suggest that the further development of PfMSP8 as a malaria vaccine component should focus on the use of PfMSP8(Delta Asn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including PfMSP1(19).