Anabe Denise, Teräsjärvi Johanna T, Barkoff Alex-Mikael, Knuutila Aapo, Pape Bernd, van Gageldonk Pieter, Buisman Annemarie, Mertsola Jussi, He Qiushui
Institute of Biomedicine, Research Centre for Infections and Immunity, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Institute of Biomedicine, Research Centre for Infections and Immunity, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Department of Life Technologies, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Vaccine. 2025 Jan 12;44:126573. doi: 10.1016/j.vaccine.2024.126573. Epub 2024 Nov 30.
Despite extensive vaccinations, pertussis remains endemic and epidemic in multiple countries. The persistence of cases can be partly attributed to the significant individual variation in vaccine responses. This study evaluated the association of baseline cytokines (before booster vaccination) on antibody concentrations to Tdap-vaccine antigens.
Healthy Finnish children (7-10y, n = 36), adolescents (11-15y, n = 37), young adults (20-34y, n = 25), and older adults (60-70y, n = 23) received a Tdap3-IPV booster. Serum antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), fimbriae 2/3, diphtheria toxoid (DT), and tetanus toxoid (TT), as well as PT neutralizing antibodies were measured before, one month, and one year after the booster. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17 A and IL-17F were determined.
The proportion of detectable and undetectable baseline cytokines varied between age groups 58.3 % of children had a higher proportion of detectable IL-5, IL-10, IL-13, and IL-17F compared to adolescents (IL-5, 37.8 %; IL-10, 48.6 %; IL-13, 48.6 %; IL-17F, 37.7 %), young adults (IL-5, 36.0 %; IL-10, 28.0 %; IL-13, 36.0 %; IL-17F, 44.0 %), and older adults (IL-5, 26.1 %; IL-10, 21.7 %; IL-13, 39.1 %; IL-17F, 30.4 %). IFN-γ had a lower detectability in children (44.4 %) and young (40.0 %) and older adults (39.1 %) in contrast to adolescents (62.2 %). IL-2 was undetectable in all age groups while the proportion of detectable IL-17 A decreased with age. A mixed model showed that undetectable baseline levels of IFN-γ, IL-2, IL-10, and IL-17 A were associated with higher antibody concentrations in children before and after vaccination, particularly against PT. Positive associations were observed in adolescents for anti-TT concentrations and young adults for anti-FHA IgA concentrations.
These findings indicate a possible role of existing cytokines in pertussis booster antibody concentrations in children and warrant further studies in different populations. However, the results should be interpreted with caution as the number of subjects is limited.
尽管进行了广泛的疫苗接种，但百日咳在多个国家仍呈地方性流行和流行性。病例的持续存在部分可归因于疫苗反应的显著个体差异。本研究评估了基础细胞因子（加强免疫前）与破伤风类毒素、白喉类毒素和无细胞百日咳疫苗（Tdap）抗原抗体浓度之间的关联。
健康的芬兰儿童（7 - 10岁，n = 36）、青少年（11 - 15岁，n = 37）、年轻成年人（20 - 34岁，n = 25）和老年人（60 - 70岁，n = 23）接受了Tdap3 - 脊髓灰质炎灭活疫苗（IPV）加强免疫。在加强免疫前、后1个月和1年后，检测血清中针对百日咳毒素（PT）、丝状血凝素（FHA）、百日咳杆菌黏附素（Prn）、2/3型菌毛、白喉类毒素（DT）和破伤风类毒素（TT）的抗体，以及PT中和抗体。测定基础血清中干扰素 - γ（IFN - γ）、白细胞介素 - 2（IL - 2）、白细胞介素 - 5（IL - 5）、白细胞介素 - 10（IL - 10）、白细胞介素 - 13（IL - 13）、白细胞介素 - 17A和白细胞介素 - 17F的浓度。
可检测和不可检测的基础细胞因子比例在各年龄组之间有所不同。与青少年（IL - 5，37.8%；IL - 10，48.6%；IL - 13，48.6%；IL - 17F，37.7%）、年轻成年人（IL - 5，36.0%；IL - 10，28.0%；IL - 13，36.0%；IL - 17F，44.0%）和老年人（IL - 5，26.1%；IL - 10，2l.7%；IL - 13，39.1%；IL - 17F，30.4%）相比，58.3%的儿童可检测到的IL - 5、IL - 10、IL - 13和IL - 17F比例更高。与青少年（62.2%）相比，IFN - γ在儿童（44.4%）、年轻成年人（40.0%）和老年人（39.1%）中的可检测性较低。所有年龄组均未检测到IL - 2，且可检测到的IL - 17A比例随年龄增长而降低。混合模型显示，IFN - γ、IL - 2、IL - 10和IL - 17A基础水平不可检测与儿童接种疫苗前后较高的抗体浓度相关，尤其是针对PT的抗体。在青少年中观察到抗TT浓度呈正相关，在年轻成年人中观察到抗FHA IgA浓度呈正相关。
这些发现表明现有细胞因子可能在儿童百日咳加强免疫抗体浓度中发挥作用，值得在不同人群中进一步研究。然而，由于受试者数量有限，对结果的解读应谨慎。
