Meraldi Valentin, Audran Régine, Romero Jackeline F, Brossard Vincent, Bauer Jacques, López José Alejandro, Corradin Giampietro
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Vaccine. 2003 Jun 2;21(19-20):2485-91. doi: 10.1016/s0264-410x(03)00093-8.
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.The strong antibody and CTL responses observed to a synthetic peptide in mice, the safety profile of the adjuvant and its extensive physico-chemical characterization suggest that OM-174 has a potential use in vaccine formulations for humans.
本项目的目标是评估一种新型的供人类使用的免疫调节佐剂OM-174，它是一种源自大肠杆菌脂多糖A的可溶性佐剂。在本研究中，我们使用了一种以安全性和可重复性著称的合成肽以及BALB/c小鼠的鼠模型。所使用的长肽（PbCS 242-310）对应于环子孢子蛋白（CSP）的C末端区域，CSP是疟原虫子孢子表面的主要蛋白。皮下注射PbCS 242-310与可溶性佐剂OM-174相结合可诱导产生持久的肽特异性抗体滴度，与用不完全弗氏佐剂（IFA）免疫所获得的滴度相当。通过IFN-γ ELISPOT分析对CD8(+) T细胞反应进行的体外评估显示，与IFA相比，注射含OM-174佐剂的多肽分别在引流淋巴结和脾脏中诱导产生了频率相似且增加了八倍的肽特异性淋巴细胞。CD8(+) T细胞对序列PbCS 245-253具有特异性，这是一个众所周知的H-2K(d)限制性CTL表位，并且如铬释放试验所示具有细胞毒性。用该多肽与佐剂OM-174联合免疫BALB/c小鼠后，在用活的伯氏疟原虫子孢子攻击后可提供保护。在小鼠中观察到对合成肽有强烈的抗体和CTL反应、佐剂的安全性概况及其广泛的物理化学特性表明，OM-174在人类疫苗制剂中具有潜在用途。
