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首页> 外文期刊>Parasites Vectors >Monoclonal antibody targeting complement C9 binding domain of Trichinella spiralis paramyosin impairs the viability of Trichinella infective larvae in the presence of complement
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Monoclonal antibody targeting complement C9 binding domain of Trichinella spiralis paramyosin impairs the viability of Trichinella infective larvae in the presence of complement

机译：靶向旋毛虫副肌球蛋白补体C9结合域的单克隆抗体会损害存在补体的旋毛虫感染性幼虫的生存能力

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Background Trichinella spiralis expresses paramyosin (Ts-Pmy) not only as a structural protein but also as an immunomodulator that inhibits host complement as a survival strategy. Previous studies demonstrated that Ts-Pmy bound to complement components C8 and C9 and inhibited the polymerization of C9 during the formation of the membrane attack complex (MAC). The C9 binding domain of Ts-Pmy was identified within 14 amino acid residues at the C-terminus of Ts-Pmy. The production of a monoclonal antibody that specifically targets the C9 binding site is necessary for further studies of Ts-Pmy function and may be used as a therapeutic agent for T. spiralis infection. Methods In this study, a monoclonal antibody against the complement C9 binding domain of Ts-Pmy (mAb 9G3) was produced using hybridoma technology. The binding activity of the mAb produced for recombinant or native Ts-Pmy and the blockade of Ts-Pmy binding to C9 by the mAb were assessed by Western blot analysis. The effect of the mAb on the viability of T. spiralis was observed by co-incubation of T. spiralis with mAb 9G3 in the presence of complement in vitro and by passive transfer of the mAb into naive mice following T. spiralis larval challenge. Results mAb 9G3 was successfully produced against the C9 binding domain of Ts-Pmy and bound specifically not only to recombinant Ts-Pmy but also to native Ts-Pmy expressed in different stages of T. spiralis, including adult worms, newborn larvae and muscle larvae. The binding of mAb 9G3 to Ts-Pmy efficiently blocked the binding of Ts-Pmy to human complement C9, resulting in a significant increase in the complement-mediated killing of newborn larvae in vitro and reduced infectivity of T. spiralis larvae in mice passively transferred with the mAb. Conclusions mAb 9G3 is a specific antibody that binds to the C9 binding domain of Ts-Pmy and interferes with Ts-Pmy’s complement-binding activity. Therefore, this mAb is a protective antibody that has potential as a preventive and therapeutic agent for T. spiralis infection.
机译：背景技术旋毛虫不仅以结构蛋白的形式表达副肌球蛋白（Ts-Pmy），而且还以抑制宿主补体的免疫调节剂的表达作为生存策略。先前的研究表明，Ts-Pmy与膜成分C8和C9结合并在膜攻击复合物（MAC）形成过程中抑制了C9的聚合。在Ts-Pmy的C末端的14个氨基酸残基内鉴定了Ts-Pmy的C9结合结构域。特异性靶向C9结合位点的单克隆抗体的产生对于Ts-Pmy功能的进一步研究是必要的，并且可以用作螺旋体感染的治疗剂。方法在本研究中，使用杂交瘤技术生产了针对Ts-Pmy的补体C9结合域的单克隆抗体（mAb 9G3）。通过Western印迹分析评估了针对重组或天然Ts-Pmy产生的mAb的结合活性以及该mAb对Ts-Pmy与C9结合的阻断作用。在体外存在补体的情况下，将螺旋藻与mAb 9G3共孵育，并在螺旋藻幼虫攻击后将mAb被动转移至幼稚小鼠中，观察到mAb对螺旋藻活力的影响。结果成功生产了针对Ts-Pmy的C9结合域的mAb 9G3，不仅与重组Ts-Pmy特异性结合，而且还与在螺旋线虫不同阶段表达的天然Ts-Pmy特异性结合，包括成虫，新生幼虫和肌肉幼虫。 。 mAb 9G3与Ts-Pmy的结合有效地阻断了Ts-Pmy与人补体C9的结合，导致补体介导的体外杀灭幼虫的杀伤力显着增加，并降低了被动转移小鼠中螺旋丝虫幼虫的感染性与单克隆抗体。结论mAb 9G3是一种特异性抗体，可与Ts-Pmy的C9结合结构域结合并干扰Ts-Pmy的补体结合活性。因此，该mAb是一种保护性抗体，具有作为螺旋藻感染的预防和治疗剂的潜力。

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