Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

尽管广泛接种疫苗，许多国家仍继续经历百日咳流行。加强疫苗接种后保护作用减弱，凸显了需要更好地了解促进持久保护的免疫因素。在这里，我们应用系统疫苗学来研究荷兰（N = 14；NL）和英国（N = 12；UK）青少年接受破伤风-白喉-无细胞百日咳灭活脊髓灰质炎病毒（Tdap-IPV）疫苗的抗体反应。我们报告说，血液中的早期抗病毒和干扰素基因表达特征与百日咳特异性抗体反应的持续性相关。对先天反应的单细胞分析确定单核细胞和髓样树突状细胞 (MoDC) 是上调抗病毒基因表达和 I 型干扰素细胞因子产生的主要反应者。根据公开数据，我们表明，与 Tdap-IPV 相比，Tdap 疫苗接种刺激的抗病毒/I 型干扰素反应显着降低，这表明 IPV 可能促进抗病毒基因表达。随后的体外刺激实验证明 MoDC 中促炎性 p38 MAP 激酶途径具有 TLR 依赖性、IPV 特异性激活。总之，我们的数据提供了对百日咳加强疫苗接种的分子宿主反应的见解，并证明 IPV 增强了与持久的百日咳特异性抗体反应相关的先天免疫活性。