Instituto de Inmunología, Universidad del Valle, Cali, Colombia.
Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):35-42. doi: 10.4269/ajtmh.2011.09-0507.
Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines in vitro. Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production in vitro upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial.
疟原虫环子孢子蛋白(CS)是一种主要的疟疾疫苗候选物。我们描述了 21 名疟原虫阴性志愿者接种用长合成肽(来源于 CS 蛋白,并用 Montanide ISA 720 配制)疫苗后引起的特异性免疫应答的特征。分析了抗体和细胞介导的免疫应答。抗体主要为 IgG1 和 IgG3 同种型,在免疫荧光抗体试验中识别寄生虫蛋白,并在体外部分阻断孢子虫侵入肝癌细胞系。来自大多数志愿者(94%)的外周血单核细胞在体外受到长信号肽和含有 CD8+ T 细胞表位的短肽刺激后产生 IFN-γ。由于样本量相对有限,无法得出与观察到的免疫反应相关的 HLA 关联的结论。总之,这些候选疫苗具有固有安全性和耐受性,以及强烈的抗体应答、入侵阻断活性和 IFN-γ产生,值得在 II 期临床试验中进一步测试。