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首页> 外文期刊>Vaccine >OM-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic C-terminal fragment 242-310 from the circumsporozoite protein of Plasmodium berghei
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OM-174, a new adjuvant with a potential for human use, induces a protective response when administered with the synthetic C-terminal fragment 242-310 from the circumsporozoite protein of Plasmodium berghei

机译:OM-174是一种具有潜在用途的新型佐剂,当与伯氏疟原虫的环子孢子蛋白的合成C端片段242-310一起给药时,可诱导保护性应答

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The goal of this project was the evaluation of a novel immunomodulatory adjuvant for human use, OM-174, which is a soluble adjuvant derived from Escherichia coli lipid A. For this study, we used a synthetic peptide, known for its safety and reproducibility and the murine model of BALB/c mice. The long peptide (PbCS 242-310) used corresponds to the C-terminal region of the circumsporozoite protein (CSP) that is the major protein on the surface of Plasmodium sporozoites. Subcutaneous injections of PbCS 242-310 in combination with soluble adjuvant OM-174 induced long lasting peptide-specific antibody titres comparable to those obtained by immunization with incomplete Freund's adjuvant (IFA). The ex vivo evaluation of the CD8(+) T cell response by IFN-gamma ELISPOT assay revealed that the injection of polypeptide with OM-174 adjuvant induced, compared to IFA, a similar and an eight-fold increased frequency of peptide-specific lymphocytes in the draining lymph-nodes and in the spleen, respectively. The CD8(+) T-cells are specific for the sequence PbCS 245-253, a well-known H-2K(d)-restricted CTL epitope, and are cytotoxic as shown in a chromium release assay. Immunization of BALB/c mice with this polypeptide in combination with adjuvant OM-174 conferred a protection after challenge with live Plasmodium berghei sporozoites.
机译:该项目的目标是评估新型人用免疫调节佐剂OM-174,它是一种衍生自大肠杆菌脂质A的可溶性佐剂。在这项研究中,我们使用了一种合成肽,该肽以其安全性,可重复性和BALB / c小鼠的鼠模型。使用的长肽(PbCS 242-310)对应于环子孢子蛋白(CSP)的C端区域,后者是疟原虫子孢子表面上的主要蛋白。皮下注射PbCS 242-310与可溶性佐剂OM-174组合可诱导持久的肽特异性抗体滴度,与通过不完全弗氏佐剂(IFA)免疫获得的滴度相当。通过IFN-γELISPOT分析对CD8(+)T细胞反应的离体评估显示,与IFA相比,OM-174佐剂注射多肽诱导的肽特异性淋巴细胞频率相似且增加了八倍在引流淋巴结和脾脏中。 CD8(+)T细胞对序列PbCS 245-253(众所周知的H-2K(d)限制性CTL表位)具有特异性,并且具有细胞毒性,如铬释放分析所示。用该多肽与佐剂OM-174联合免疫BALB / c小鼠后,用活的伯氏疟原虫子孢子激发后可提供保护。

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