Lambert Eleonora E, Corbière Véronique, van Gaans-van den Brink Jacqueline A M, Duijst Maxime, Venkatasubramanian Prashanna Balaji, Simonetti Elles, Huynen Martijn, Diavatopoulos Dimitri D, Versteegen Pauline, Berbers Guy A M, Mascart Françoise, van Els Cécile A C M
Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands.
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), 1070 Brussels, Belgium.
Vaccines (Basel). 2020 May 15;8(2):225. doi: 10.3390/vaccines8020225.
To advance research and development of improved pertussis vaccines, new immunoassays are needed to qualify the outcome of (Bp) specific CD4+ T-cell differentiation. Here, we applied a recently developed whole blood assay to evaluate Bp specific CD4+ T-cell responses. The assay is based on intracellular cytokine detection after overnight Bp antigen stimulation of diluted whole blood. We show for the first time that CD4+ T-cell memory of Th1, Th2, and Th17 lineages can be identified simultaneously in whole blood. Participants ranging from 7 to 70 years of age with different priming backgrounds of whole-cell pertussis (wP) and acellular pertussis (aP) vaccination were analyzed around an acellular booster vaccination. The assay allowed detection of low frequent antigen-specific CD4+ T-cells and revealed significantly elevated numbers of activated and cytokine-producing CD4+ T-cells, with a significant tendency to segregate recall responses based on primary vaccination background. A stronger Th2 response hallmarked an aP primed cohort compared to a wP primed cohort. In conclusion, analysis of Bp specific CD4+ T-cell responses in whole blood showed separation based on vaccination background and provides a promising tool to assess the quantity and quality of CD4+ T-cell responses induced by vaccine candidates.
为推动改进型百日咳疫苗的研发，需要新的免疫测定法来鉴定百日咳博德特氏菌（Bp）特异性CD4+ T细胞分化的结果。在此，我们应用了一种最近开发的全血检测法来评估Bp特异性CD4+ T细胞反应。该检测法基于对稀释全血进行过夜Bp抗原刺激后检测细胞内细胞因子。我们首次表明，可在全血中同时鉴定出Th1、Th2和Th17谱系的CD4+ T细胞记忆。在无细胞百日咳疫苗加强免疫前后，对年龄在7至70岁之间、具有不同全细胞百日咳（wP）和无细胞百日咳（aP）疫苗接种初免背景的参与者进行了分析。该检测法能够检测到低频抗原特异性CD4+ T细胞，并显示出活化的和产生细胞因子的CD4+ T细胞数量显著增加，且根据初次接种背景有明显的区分回忆反应的趋势。与wP初免队列相比，更强的Th2反应是aP初免队列的标志。总之，对全血中Bp特异性CD4+ T细胞反应的分析显示出基于疫苗接种背景的区分，并为评估候选疫苗诱导的CD4+ T细胞反应的数量和质量提供了一种有前景的工具。
