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首页> 外文期刊>Infection and immunity >Potent Malaria Transmission-Blocking Antibody Responses Elicited by Plasmodium falciparum Pfs25 Expressed in Escherichia coli after Successful Protein Refolding
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Potent Malaria Transmission-Blocking Antibody Responses Elicited by Plasmodium falciparum Pfs25 Expressed in Escherichia coli after Successful Protein Refolding

机译：成功的蛋白质复性后，由大肠杆菌表达的恶性疟原虫Pfs25引起的强效疟疾传播阻断抗体反应

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Production of Pfs25, a Plasmodium falciparum transmission-blocking vaccine target antigen, in functional conformation with the potential to elicit effective immunogenicity still remains a major challenge. In the current study, codon-harmonized recombinant Pfs25 (CHrPfs25) was expressed in Escherichia coli, and purified protein after simple oxidative refolding steps retained reduction-sensitive conformational epitopes of transmission-blocking monoclonal antibodies. CHrPfs25 formulated in several adjuvants elicited strong immunogenicity in preclinical studies in mice. Antibodies elicited after immunization recognized native Pfs25 on the surface of live gametes of P. falciparum and demonstrated complete malaria transmission-blocking activity. The transmission-blocking efficacy was 100% even after a 1:128 dilution of sera from immunized mice in the complete Freund's adjuvant and Montanide ISA51 groups and after a 1:16 dilution of sera from mice in the alum group. The blocking was mediated by antibodies; purified IgG at concentrations as low as 31.25 μg/ml exhibited 100% transmission blocking in membrane feeding assays employing two different species of mosquitoes, Anopheles gambiae and Anopheles stephensi. This study provides the first evidence for successful expression of biologically functional rPfs25 in E. coli. The extremely potent malaria transmission-blocking activity of antibodies elicited by immunization with purified protein provides strong support for further evaluation of E. coli-derived CHrPfs25 as a malaria transmission-blocking vaccine in human clinical trials.
机译：具有潜在的引起有效免疫原性的功能构象的Pfs25（恶性疟原虫传播阻断疫苗靶抗原）的生产仍然是主要挑战。在当前的研究中，密码子协调的重组Pfs25（CHrPfs25）在大肠杆菌中表达，纯化的蛋白质经过简单的氧化重折叠步骤后，保留了阻滞传输的单克隆抗体的还原敏感构象表位。在几种佐剂中配制的CHrPfs25在小鼠的临床前研究中具有很强的免疫原性。免疫后引发的抗体识别恶性疟原虫活配子表面上的天然Pfs25，并显示出完全的疟疾传播阻断活性。完全弗氏佐剂和Montanide ISA51组中免疫小鼠的血清按1：128稀释后，明矾组小鼠的血清按1:16稀释后，其阻断传输的效率为100％。阻断是由抗体介导的。在使用两种不同种类的蚊子冈比亚按蚊和斯蒂芬按蚊的膜进食试验中，低至31.25μg/ ml的纯化IgG表现出100％的传输阻断。这项研究提供了在大肠杆菌中成功表达生物学功能的rPfs25的第一个证据。通过纯化蛋白免疫产生的抗体的极强的疟疾传播阻断活性为人类临床试验中进一步评估大肠杆菌来源的CHrPfs25作为一种疟疾传播阻断疫苗提供了有力支持。

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