Whole-cell inactivated vaccine against Bordetella pertussis (wP) was substituted in many countries by an acellular subunit vaccine (aP) to reduce side effects. Recent epidemiological studies have shown that aP vaccination in infancy induces less durable immunity than wP vaccination. To determine immunological differences associated with aP vs. wP priming, we performed system-level profiling of the immune response in adults primed with aP vs. wP vaccine in infancy following the Tdap booster vaccination as a surrogate to antigen encounter in vivo. Shared immune responses across cohorts were identified, including an increase of the blood monocyte frequency on day 1, and strong antigen-specific IgG response seven days after boost. Comparing aP and wP primed individuals, we found a subset of aP-primed individuals with higher levels of expression for several genes including CCL3 on day 3 and NFKBIA and ICAM1 on day 7 post immunization. These observations were supported by increased CCL3 concentrations in plasma of aP primed individuals. Contrary to the wP individuals, the CCL3-high aP subset presented boosted PT-specific IgE responses. Furthermore, higher antigen specific IgG4 and IgG3 antibodies against specific vaccine antigens at baseline and post boost of aP individuals was observed, suggesting a long term maintained difference in the IgG subtype response. Overall our findings demonstrate that, while broad immune response patterns to Tdap boost overlap between aP and wP primed individuals, a subset of aP primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

中文翻译：

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用婴儿全细胞疫苗和脱细胞疫苗接种的成人百日咳博德特氏菌加强疫苗反应的系统视图

在许多国家，针对百日咳博德特氏菌（wP）的全细胞灭活疫苗被无细胞亚单位疫苗（aP）替代，以减少副作用。最近的流行病学研究表明，婴儿期接种aP疫苗比wP疫苗诱导的持久性免疫力差。为了确定与aP vs. wP引发相关的免疫学差异，我们在婴儿期进行Tdap加强疫苗接种后，对体内接种aP vs. wP疫苗的成年人进行了免疫应答的系统级分析，以作为体内抗原接触的替代方法。跨队列的免疫应答得到确认，包括第1天血液单核细胞频率增加，以及加强免疫后7天强烈的抗原特异性IgG反应。比较aP和wP启动的个人，我们发现了aP致敏个体的子集，这些个体的一些基因表达水平较高，包括免疫后第3天的CCL3和免疫后7天的NFKBIA和ICAM1。这些观察结果得到了aP启动个体血浆中CCL3浓度增加的支持。与wP个体相反，CCL3高aP子集表现出增强的PT特异性IgE反应。此外，在aP个体的基线和加强免疫后观察到针对特定疫苗抗原的更高抗原特异性IgG4和IgG3抗体，这表明IgG亚型应答中长期保持差异。总的来说，我们的发现表明，尽管对Tdap的广泛免疫应答模式增强了aP和wP致敏个体之间的重叠，但aP致敏个体的子集却呈现出不同的应答。