The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens
The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens
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DOI：
10.1016/j.vaccine.2004.03.007
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发表时间：
2004-09-03
期刊：
影响因子：
5.5
通讯作者：
Zauner, W
中科院分区：
文献类型：
--
作者：
Fritz, JH;Brunner, S;Zauner, W
阳离子抗菌肽 (CAMP) 是先天免疫系统的主动防御成分。几种人工 CAMP 已被设计为抗生素肽疗法，但没有报道称它们在动物模型中发挥佐剂活性。在这里，我们首次证明人工 CAMP KLKLLLLLKLK (KLKL5KLK) 是体内共注射抗原的适应性免疫的有效诱导剂。 KLKL5KLK与模型抗原卵清蛋白（OVA）或市售流感疫苗共注射后获得高水平的抗原特异性抗体。我们发现，当与蛋白质和肽抗原共同注射时，KLKL5KLK 会诱导持续的免疫反应，并具有普遍的 T(H)2 特征。此外，当 C 端酰胺化或合成为逆向全 D 肽时，肽 KLKL5KLK 的免疫增强活性得以保留。我们提供的证据表明，KLKL5KLK 增强了抗原与抗原呈递细胞的结合，并在注射部位形成抗原库，使其成为新型疫苗设计的有趣佐剂。 (C) 2004 Elsevier Ltd. 保留所有权利。
Cationic antimicrobial peptides (CAMPs) are active defence components of the innate immune system. Several artificial CAMPs have been designed as antibiotic peptide therapeutics, but none have been reported to exert adjuvant activity in animal models. Here we show for the first time that an artificial CAMP, KLKLLLLLKLK (KLKL5KLK), is a potent inducer of adaptive immunity to co-injected antigens in vivo. High levels of antigen-specific antibodies were obtained after co-injection of KLKL5KLK with the model antigen ovalbumin (OVA) or a commercially available influenza vaccine. We show that KLKL5KLK induces a sustained immune response with a prevalent T(H)2 profile when co-injected with proteinaceous and peptide-based antigens. Furthermore, the immuno-enhancing activity of peptide KLKL5KLK was retained when C-terminally amidated or synthesised as retro-all-D-peptide. We provide evidence that KLKL5KLK enhances the association of antigen to antigen-presenting cells and forms a depot of antigen at the site of injection, making it an interesting adjuvant for novel vaccine design. (C) 2004 Elsevier Ltd. All rights reserved.