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Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier.

机译:通过破伤风类毒素载体的预免疫增强了对合成人疟疾肽的表位反应。

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Successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier. Tetanus toxoid (TT) has been proposed because of its safe and widespread use in humans. Paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier. Indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine made with a streptococcal peptide conjugated to TT. Our present study shows that similar results can be observed in mice preimmunized with TT 1 month before the administration of a conjugate containing TT and a Plasmodium knowlesi peptide. Analysis of the isotypic pattern of the antipeptide response showed that the immunoglobulin G1 (IgG1) subclass and especially the IgG2a and IgG2b subclasses were suppressed. In contrast, when a sporozoite peptide from Plasmodium falciparum was coupled to TT, the total antipeptide antibodies and particularly the IgG1 subclass were enhanced by preimmunization by TT. This increase of antipeptide antibodies was correlated with a greater ability of the sera to neutralize sporozoite infectivity. These results indicate that prior exposure to TT does not systematically impair the antibody response against a peptide administered as a peptide-TT conjugate.
机译:合成的疟疾子孢子肽对人类的成功疫苗接种可能取决于适当载体的选择。已经提出了破伤风类毒素(TT),因为它在人类中安全且广泛使用。然而,自相矛盾的是,事先暴露于这种类毒素疫苗可能会产生特异性的表位抑制作用,以抑制与该蛋白作为载体结合的合成疟疾肽。实际上,我们以前已经报道过,在用链球菌肽与TT偶联制成的合成疫苗的情况下会发生这种现象。我们目前的研究表明,在给予含TT和诺氏疟原虫肽的结合物1个月前,用TT预免疫的小鼠中可以观察到类似的结果。分析抗肽应答的同型模式表明,免疫球蛋白G1(IgG1)亚类,尤其是IgG2a和IgG2b亚类受到抑制。相反,当恶性疟原虫的子孢子肽与TT偶联时,通过TT预免疫增强了总的抗肽抗体,特别是IgG1亚类。抗肽抗体的这种增加与血清中和子孢子感染性的更大能力有关。这些结果表明,事先暴露于TT不会系统地削弱针对作为肽-TT缀合物施用的肽的抗体应答。

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