Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B-Single-Chain Fv Fusion Protein
Antimalarial Activity of Granzyme B and Its Targeted Delivery by a Granzyme B-Single-Chain Fv Fusion Protein
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DOI：
10.1128/aac.04190-14
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发表时间：
2015-01-01
影响因子：
4.9
通讯作者：
Fendel, Rolf
中科院分区：
文献类型：
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作者：
Kapelski, Stephanie;de Almeida, Melanie;Fendel, Rolf
我们在此首次提出颗粒酶B对恶性疟原虫起作用的证据（50%抑制浓度[IC50]， 1,590 nM； 95%置信区间[95% CI]， 1,197至2,112 nM）。我们创造了一种新的抗疟疾融合蛋白，由颗粒酶B与merozoite表面蛋白4 （MSP4）特异性单链Fv蛋白（scFv）融合组成，该蛋白将酶靶向感染红细胞，IC50降低了8倍（176 nM; 95% CI， 154至202 nM）。本研究证实了以颗粒酶B为基础的重组抗体介导的抗疟疾免疫疗法的治疗效果。
We present here the first evidence that granzyme B acts against Plasmodium falciparum (50% inhibitory concentration [IC50], 1,590 nM; 95% confidence interval [95% CI], 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC50 (176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.