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

Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine.
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DOI:
10.4049/jimmunol.1102710
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发表时间:
2012-05-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Riley EM
Riley EM
中科院分区:
其他
文献类型:
--
作者:
Horowitz A;Hafalla JC;King E;Lusingu J;Dekker D;Leach A;Moris P;Cohen J;Vekemans J;Villafana T;Corran PH;Bejon P;Drakeley CJ;von Seidlein L;Riley EM

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RTS,S/AS 01是一种针对恶性疟原虫红细胞前期阶段的疫苗,正在进行临床试验。我们报告了一项IIb期RTS,S/AS 01 E试验中坦桑尼亚儿童对RTS,S -B肝炎表面抗原(HBs)和恶性疟原虫环子孢子(CS)蛋白组分抗原的细胞免疫应答分析。RTS,S/AS 01 E疫苗对HBs肽的T细胞IFN-γ、CD 69和CD 25应答比对照强,表明RTS,S增强了预先存在的HBs应答。RTS、S疫苗接种增强了T细胞CD 69和CD 25对CS和CS特异性分泌的IL-2的应答。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CD 69对HBs肽的应答的幅度与分泌的IL-2浓度相关。CD 69和CD 25表达和IL-2分泌可能代表RTS、S诱导的CS特异性T细胞的敏感标志物。T细胞来源的IL-2在RTS、S疫苗接种个体中增强NK细胞活化的潜力,以及这与保护的相关性,需要进一步探索。
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.
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