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Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTSS/AS01 malaria vaccine

机译:抗原特异性IL-2分泌物与坦桑尼亚儿童与RTSS / AS01疟疾疫苗免疫后的NK细胞反应相关

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摘要

RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials. We report an analysis of cellular immune response to component antigens of RTS,S – hepatitis B surface antigen (HBs) and P. falciparum circumsporozoite (CS) protein – among Tanzanian children in a Phase IIb RTS,S/AS01E trial. RTS,S/AS01 E vaccinees make stronger T cell IFN-γ, CD69 and CD25 responses to HBs peptides than do controls, indicating that RTS,S boosts pre-existing HBs responses. T cell CD69 and CD25 responses to CS and CS-specific secreted IL-2, were augmented by RTS,S vaccination. Importantly, more than 50% of peptide-induced IFN-γ+ lymphocytes were NK cells and the magnitude of the NK cell CD69 response to HBs peptides correlated with secreted IL-2 concentration. CD69 and CD25 expression and IL-2 secretion may represent sensitive markers of RTS,S-induced, CS-specific T cells. The potential for T cell-derived IL-2 to augment NK cell activation in RTS,S-vaccinated individuals, and the relevance of this for protection, needs to be explored further.
机译:RTS,S / AS01,靶向疟原虫前红细胞阶段的疫苗正在进行临床试验。我们报告了对RTS,S - 乙型肝炎表面抗原(HBS)和P.Malciparum环孢子(CS)蛋白 - 在IIB RTS,S / AS01E试验中的坦桑儿儿童中的细胞免疫反应的分析。 RTS,S / AS01疫苗疫苗使T细胞IFN-γ,CD69和CD25对HBS肽的反应比对照组成,表明RTS,S促进了预先存在的HBS反应。 T细胞CD69和CD25对Cs和Cs特异性分泌的IL-2的反应被RTS,S疫苗接种增强。重要的是,超过50%的肽诱导的IFN-γ + 淋巴细胞是NK细胞,并且NK细胞CD69对HBS肽的响应与分泌的IL-2浓度相关的响应。 CD69和CD25表达和IL-2分泌物可以代表RTS,S诱导的CS特异性T细胞的敏感标志物。需要进一步探索T细胞衍生的IL-2在RTS,S疫苗的个体中增加NK细胞活化的潜力,以及这种用于保护的相关性。

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