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经评估,用疟原虫 MSP-1 定点设计假肽-BSA 缀合物诱导产生的兔 F(ab')2'抗体片段,可经被动传递在啮齿动物模型中提供抗疟疾保护作用。

Protection against malaria is conferred by passive transferring rabbit F(ab)(2)' antibody fragments, induced by Plasmodium falciparum MSP-1 site-directed designed pseudopeptide-BSA conjugates assessed in a rodent model.

机构信息

Fundación Instituto de Inmunología de Colombia and Universidad del Rosario, Bogotá, DC, Colombia.

出版信息

Mol Immunol. 2011 Jan;48(4):657-69. doi: 10.1016/j.molimm.2010.11.007. Epub 2010 Dec 4.

Abstract

F(ab)(2)'-immunoglobulin (Ig) fragments induced by site-directed designed immunogens are emerging as novel tools of potential utility in the treatment of clinical episodes of transmissible diseases such as malaria. Immunogens based on reduced amide pseudopeptides based on site-directed molecular modifications represent structural probes that could be considered as novel vaccine candidates, as we have previously demonstrated. We have obtained F(ab)(2)'-Ig rabbit antibodies induced against the N-terminal sequence of the native Merozoite Surface Protein-1 (MSP-1) of Plasmodium falciparum and a set of five MSP-1-derived reduced amide pseudopeptides. Pseudopeptides were designed for inducing functional neutralizing mono-specific polyclonal antibodies with potential applications in the control of malaria. Following a classical enzyme immunoglobulin fractionation, F(ab)(2)'-Ig fragments were tested for their ability to suppress blood-stage parasitemia by passive immunization in malaria-infected mice. Some of these fragments proved totally effective in suppressing a lethal blood-stage challenge infection and others reduced malarial parasitemia. These data suggest that protection against Plasmodium yoelii malaria following passive transfer of structurally well-defined β-strand F(ab)(2)'-Ig fragments can be associated with specific immunoglobulins induced by site-directed designed MSP-1 reduced amide pseudopeptides.

摘要

基于定点分子修饰的还原酰胺假肽的免疫原代表了结构探针,可被视为新型候选疫苗,正如我们之前所证明的那样。我们已经获得了针对恶性疟原虫(Plasmodium falciparum)原生裂殖子表面蛋白-1(MSP-1)N 端序列的 F(ab)(2)'-Ig 兔抗体和一组五个源自 MSP-1 的还原酰胺假肽。这些假肽是为诱导具有潜在疟疾控制应用的功能性中和单特异性多克隆抗体而设计的。经过经典的酶免疫球蛋白分级分离,F(ab)(2)'-Ig 片段通过被动免疫在感染疟疾的小鼠中测试其抑制血期寄生虫血症的能力。其中一些片段被证明完全有效抑制致死性血期挑战感染,而其他片段则降低了疟疾寄生虫血症。这些数据表明,结构上明确的β-折叠 F(ab)(2)'-Ig 片段的被动转移可与由定点设计的 MSP-1 还原酰胺假肽诱导的特异性免疫球蛋白相关联,从而对约氏疟原虫疟疾产生保护作用。

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