DataSheet_1_BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists.zip

BackgroundVaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children.
AimTo investigate heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.
MethodsA whole blood stimulation assay was used to investigate in vitro cytokine responses to heterologous stimulants (killed pathogens, Toll-like receptor ligands) and SARS-CoV-2 antigens. Samples from 29 children, aged 5-11 years, before and 28 days after a second BNT162b2 vaccination were analysed (V2 + 28). Samples from eight children were analysed six months after BNT162b2 vaccination.
ResultsAt V2 + 28, interferon-γ and monocyte chemoattractant protein-1 responses to S. aureus, E. coli, L. monocytogenes, BCG vaccine, H. influenzae, hepatitis B antigen, poly(I:C) and R848 stimulations were decreased compared to pre-vaccination. For most of these heterologous stimulants, IL-6, IL-15 and IL-17 responses were also decreased. There were sustained decreases in cytokine responses to viral, but not bacterial, stimulants six months after BNT162b2 vaccination. Cytokine responses to irradiated SARS-CoV-2, and spike glycoprotein subunits (S1 and S2) were increased at V2 + 28 for most cytokines and remained higher than pre-vaccination responses 6 months after BNT162b2 vaccination for irradiated SARS-CoV-2 and S1. There was no correlation between BNT162b2 vaccination-induced anti-SARS-CoV2-receptor binding domain IgG antibody titre at V2 + 28 and cytokine responses.
ConclusionsBNT162b2 vaccination in children alters cytokine responses to heterologous stimulants, particularly one month after vaccination. This study is the first to report the immunological heterologous effects of COVID-19 vaccination in children.

### 研究背景
疫苗可产生有益的脱靶异源（heterologous）效应，该效应可改变机体对无关感染的免疫应答，并发挥抗感染保护作用。目前尚无针对儿童群体的新冠疫苗异源效应相关研究。

### 研究目的
本研究旨在探究BNT162b2型新冠疫苗在儿童群体中产生的异源免疫效应与特异性免疫效应。

### 研究方法
采用全血刺激实验，体外检测针对异源刺激物（灭活病原体、Toll样受体配体）与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗原的细胞因子应答水平。本研究分析了29名5至11岁儿童在接种第二剂BNT162b2疫苗前，以及接种后28天（记为V2+28）的血液样本；同时分析了8名儿童在接种BNT162b2疫苗6个月后的血液样本。

### 研究结果
在V2+28时间点，相较于疫苗接种前，针对金黄色葡萄球菌（S. aureus）、大肠埃希菌（E. coli）、单核细胞增生李斯特菌（L. monocytogenes）、卡介苗（BCG vaccine）、流感嗜血杆菌（H. influenzae）、乙型肝炎抗原、聚肌胞苷酸（poly(I:C)）与R848刺激的干扰素-γ（interferon-γ）与单核细胞趋化蛋白-1（monocyte chemoattractant protein-1）应答水平均出现下降。针对上述多数异源刺激物，白细胞介素-6（IL-6）、白细胞介素-15（IL-15）与白细胞介素-17（IL-17）的应答水平同样出现下降。在接种BNT162b2疫苗6个月后，机体针对病毒类刺激物的细胞因子应答水平仍持续下降，但针对细菌类刺激物的应答无此变化。在V2+28时间点，针对灭活严重急性呼吸综合征冠状病毒2（irradiated SARS-CoV-2）与刺突糖蛋白亚基（S1、S2）的多数细胞因子应答水平均出现升高；且在接种疫苗6个月后，针对灭活SARS-CoV-2与S1亚基的细胞因子应答水平仍高于疫苗接种前。在V2+28时间点，BNT162b2疫苗诱导产生的抗SARS-CoV-2受体结合域IgG抗体滴度与细胞因子应答水平无相关性。

### 研究结论
儿童接种BNT162b2疫苗可改变其针对异源刺激物的细胞因子应答，尤其在接种后1个月时最为显著。本研究首次报道了新冠疫苗在儿童群体中产生的免疫异源效应。