da Silva Antunes Ricardo, Soldevila Ferran, Pomaznoy Mikhail, Babor Mariana, Bennett Jason, Tian Yuan, Khalil Natalie, Qian Yu, Mandava Aishwarya, Scheuermann Richard H, Cortese Mario, Pulendran Bali, Petro Christopher D, Gilkes Adrienne P, Purcell Lisa A, Sette Alessandro, Peters Bjoern
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
J. Craig Venter Institute, La Jolla, California, USA.
JCI Insight. 2021 Apr 8;6(7):141023. doi: 10.1172/jci.insight.141023.
The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show 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.
全球百日咳发病率上升表明，目前针对百日咳博德特氏菌感染的疫苗接种在保护质量和持续时间方面存在局限性。感染的再次出现与无细胞疫苗（aP）的引入有关，与之前使用的全细胞（wP）疫苗相比，无细胞疫苗的安全性有所提高。为了确定婴儿期aP和wP初免之间的免疫差异，我们对加强免疫的免疫反应进行了系统研究。转录组学、蛋白质组学、细胞计数和血清学分析揭示了不同队列中具有不同动力学的多种共同免疫反应，包括血液单核细胞频率增加和强烈的抗原特异性IgG反应。此外，我们发现aP初免个体中有一个显著的亚群（30%）具有强烈的差异特征，包括CCL3、NFKBIA和ICAM1的表达水平较高。与wP个体相反，该亚群在加强免疫后显示出PT特异性IgE反应增加，并且在基线和加强免疫后针对FHA和FIM2/3的抗原特异性IgG4和IgG3抗体水平更高。总体而言，结果表明，虽然aP和wP初免个体对Tdap加强免疫的广泛免疫反应模式重叠，但aP初免个体的一个亚群呈现出不同的反应。这些发现为研究aP疫苗接种后免疫减弱的原因和相关性提供了候选靶点。
