Anti-MSP11 IgG inhibits Plasmodium falciparum merozoite invasion into erythrocytes in vitro
Anti-MSP11 IgG inhibits Plasmodium falciparum merozoite invasion into erythrocytes in vitro
复制标题
抗 MSP11 IgG 体外抑制恶性疟原虫裂殖子侵入红细胞
DOI：
10.1016/j.parint.2018.10.012
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发表时间：
2019
影响因子：
1.9
通讯作者：
Tsuboi Takafumi
中科院分区：
文献类型：
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作者：
Tohmoto Tatsuhiro;Takashima Eizo;Takeo Satoru;Morita Masayuki;Nagaoka Hikaru;Udomsangpetch Rachanee;Sattabongkot Jetsumon;Ishino Tomoko;Torii Motomi;Tsuboi Takafumi
裂殖子表面蛋白（MSP）被认为是有前途的血液阶段疟疾疫苗候选者。MSP 3的疫苗候选性已被长期评估，然而，MSP 3家族的其他成员的候选性尚未得到充分表征。在这里，我们调查了恶性疟原虫MSP 11（PF3D7_1036000），MSP 3家族的成员，其作为血液阶段疫苗候选者的潜力。利用麦胚无细胞系统表达了MSP 3家族成员中特有的全长蛋白（MSP 11-FL）和N端半MSP 11（MSP 11-N），并用于在兔体内产生抗体。用抗MSP 11-N抗体探测的双鞭毛体裂解物的免疫印迹分析检测到约40和60 kDa的双条带，与先前的报道一致，从而证实了抗体特异性。然而，与先前报道的裂殖子表面定位不一致，免疫荧光分析（IFA）显示MSP 11可能定位于成熟裂殖子中裂殖子的棒状体颈部。入侵后，MSP 11定位于寄生虫空泡，此后在Maurer的分裂滋养体。无症状组的抗MSP 11-FL抗体水平显著高于无症状组。在疟疾低流行的泰国，这再次证实了抗MSP 11抗体在预防临床疟疾方面发挥重要作用，如先前报道的那样。此外，体外生长抑制测定显示抗MSP 11-FL兔抗体通过抑制裂殖子侵入红细胞而发挥生物学功能。这些发现进一步支持了MSP 11的疫苗候选资格。
Merozoite surface proteins (MSPs) are considered as promising blood-stage malaria vaccine candidates. MSP3 has long been evaluated for its vaccine candidacy, however, the candidacy of other members of MSP3 family is insufficiently characterized. Here, we investigated Plasmodium falciparum MSP11 (PF3D7_1036000), a member of the MSP3 family, for its potential as a blood-stage vaccine candidate. The full-length protein (MSP11-FL) as well as the N-terminal half-MSP11 (MSP11-N), known to be unique among the MSP3 family members, were expressed by wheat germ cell-free system, and used to raise antibodies in rabbit. Immunoblot analysis of schizont lysates probed with anti-MSP11-N antibodies detected double bands at approximately 40 and 60 kDa, consistent with the previous report thus confirming antibodies specificity. However, inconsistent with previously reported merozoite's surface localization, immunofluorescence assay (IFA) revealed that MSP11 likely localizes to rhoptry neck of merozoites in mature schizonts. After invasion, MSP11 localized to parasitophorous vacuole and thereafter in Maurer's clefts in trophozoites. Anti-MSP11-FL antibody levels were significantly higher in asymptomatic than symptomaticP. falciparumcases in malaria low endemic Thailand. This reconfirmed that anti-MSP11 antibodies play an important role in protection against clinical malaria, as previously reported. Furthermore, in vitro growth inhibition assay revealed that anti-MSP11-FL rabbit antibodies biologically function by inhibiting merozoite invasion of erythrocytes. These findings further support the vaccine candidacy of MSP11.