Kapelski Stephanie, de Almeida Melanie, Fischer Rainer, Barth Stefan, Fendel Rolf
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany.
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany Institute for Applied Medical Engineering at RWTH Aachen University Hospital, Department of Experimental Medicine and Immunotherapy, Aachen, Germany.
Antimicrob Agents Chemother. 2015 Jan;59(1):669-72. doi: 10.1128/AAC.04190-14. Epub 2014 Oct 13.
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.
我们在此展示了首个证据，即颗粒酶B对恶性疟原虫具有作用（半数抑制浓度[IC50]为1590 nM；95%置信区间[95%CI]为1197至2112 nM）。我们构建了一种新型抗疟融合蛋白，该蛋白由与裂殖子表面蛋白4（MSP4）特异性单链Fv蛋白（scFv）融合的颗粒酶B组成，可将该酶靶向感染的红细胞，IC50降低了多达8倍（176 nM；95%CI为154至202 nM）。本研究证实了基于颗粒酶B的重组抗体介导的抗疟免疫疗法的治疗效果。
