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首页> 外文期刊>Infection and immunity >Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites.
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Monoclonal antibodies of three different immunoglobulin G isotypes produced by immunization with a synthetic peptide or native protein protect mice against challenge with Plasmodium yoelii sporozoites.

机译：通过合成肽或天然蛋白免疫产生的三种不同免疫球蛋白G同种型的单克隆抗体可保护小鼠免受约氏疟原虫子孢子的攻击。

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Passive transfer of monoclonal antibodies (MAbs) against malaria circumsporozoite (CS) proteins protects animals against malaria. Active immunization with synthetic or recombinant peptides induces a level of polyclonal antibodies to sporozoites comparable to those found after passive immunization but does not provide comparable protection. In the Plasmodium yoelii system, synthetic or recombinant peptide-induced antibodies have never been shown to protect. The current studies were designed to determine whether immunogen structure (native protein versus synthetic peptide) or immunoglobulin G (IgG) subclass of antibodies was responsible for the absolute differences between protective, passively transferred MAbs and nonprotective, actively induced polyclonal antibodies. In this study we produced two MAbs, QGP-S1 (IgG1) and QGP-S2 (IgG2b), by immunization with a synthetic peptide based on the P. yoelii CS major repeat, (QGPGAP)4, conjugated to keyhole limpet hemocyanin. These MAbs were compared tp NYS1 (IgG3), an anti-CS protein MAb previously produced by immunization with irradiated P. yoelii sporozoites, which recognizes (QGP GAP)2. QGP-S1 and QGP-S2 passively transferred protection. However, when compared with NYS1, there was a hierarchy of protection, NYS1 > QGP-S1 > QGP-S2. There was no correlation between antibody level at challenge as determined by immunofluorescent antibody test against sporozoites or enzyme-linked immunosorbent assay against (QGPGAP)2 or apparent antibody avidity for (QGPGAP)2 by sodium thiocyanate elution assay. The data demonstrate that a synthetic peptide can induce protective antibodies and that a specific antibody subclass is not required for protection. Work to determine whether antibody affinity or fine specificity can explain the hierarchy of protection among the MAbs is under way.
机译：针对疟疾环子孢子（CS）蛋白的单克隆抗体（MAb）的被动转移可保护动物免受疟疾侵袭。用合成或重组肽主动免疫诱导的子孢子多克隆抗体水平可与被动免疫后发现的水平相当，但不能提供类似的保护作用。在约氏疟原虫系统中，从未显示出合成的或重组的肽诱导的抗体能起到保护作用。当前的研究旨在确定抗体的免疫原结构（天然蛋白还是合成肽）或免疫球蛋白G（IgG）亚类是造成保护性，被动转移的单克隆抗体和非保护性，主动诱导的多克隆抗体之间绝对差异的原因。在这项研究中，我们通过与约氏疟原虫CS主要重复序列（QGPGAP）4偶联到匙孔血蓝蛋白上的合成肽免疫，产生了两种单克隆抗体QGP-S1（IgG1）和QGP-S2（IgG2b）。将这些MAb与tp NYS1（IgG3）进行了比较，后者是一种抗CS蛋白MAb，以前是用经识别的（QGP GAP）2照射的约氏疟原虫子孢子免疫后产生的。 QGP-S1和QGP-S2被动转移保护。但是，与NYS1相比，有一个保护等级，即NYS1> QGP-S1> QGP-S2。通过针对子孢子的免疫荧光抗体测试或针对（QGPGAP）2的酶联免疫吸附测定或通过硫氰酸钠洗脱测定法对（QGPGAP）2的表观抗体亲和力确定的攻击抗体水平之间没有相关性。数据表明合成的肽可以诱导保护性抗体，并且保护不需要特定的抗体亚类。确定抗体亲和力或精细特异性是否可以解释单克隆抗体之间的保护等级的工作正在进行中。

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