PDF(Pubmed)
Abstract：
BACKGROUND: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children.
METHODS: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining.
RESULTS: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens.
CONCLUSIONS: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19.
BACKGROUND: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
METHODS: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining.
RESULTS: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens.
CONCLUSIONS: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19.
BACKGROUND: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
摘要：
背景：由疫苗接种和自然感染引起的对SARS-CoV-2的混合免疫，在儿科人群中仍然没有得到足够的理解，尽管接种疫苗的儿童中突破性感染率上升。
方法：我们进行了一项前瞻性纵向研究，特异性，在一组5-11岁的mRNA疫苗接种儿童（n=29）中，突破性SARS-CoV-2感染引起的抗原特异性T细胞反应的细胞因子谱。这项纵向分析涉及疫苗接种后16个月的六个不同时间点，在此期间，我们共分析了159份血液样本。所有随访至少12个月的儿童（n=26）经历了突破性感染。我们使用最少的血液样本进行了细胞因子释放测定，我们通过细胞内细胞因子染色验证了这些反应的细胞起源。
结果：突破性感染后，接受mRNA疫苗治疗的儿童表现出增强的Spike肽特异性Th1应答.此外,它们的Spike特异性T细胞表现出独特的CD4+IFN-γ+IL10+细胞富集，类似于具有混合免疫的成年人的特征。重要的是,疫苗接种不会阻碍靶向膜的多特异性T细胞反应的发展，核蛋白,和ORF3a/7/8抗原。
结论：儿童，先前使用基于Spike的mRNA疫苗并经历有症状或无症状的突破性感染，保留了增强和多样化Th1/IL-10抗原特异性T细胞对多种SARS-CoV-2蛋白的反应的能力。这些发现反映了与成人混合细胞免疫相关的特征，已知赋予对严重COVID-19的抗性。
背景：本研究由新加坡国家医学研究委员会（NMRC）资助（COVID19RF-0019，MOH-000019，MOH-000535，OFLCG19May-0034和MOH-OFYIRG19nov-0002）。
方法：我们进行了一项前瞻性纵向研究，特异性，在一组5-11岁的mRNA疫苗接种儿童（n=29）中，突破性SARS-CoV-2感染引起的抗原特异性T细胞反应的细胞因子谱。这项纵向分析涉及疫苗接种后16个月的六个不同时间点，在此期间，我们共分析了159份血液样本。所有随访至少12个月的儿童（n=26）经历了突破性感染。我们使用最少的血液样本进行了细胞因子释放测定，我们通过细胞内细胞因子染色验证了这些反应的细胞起源。
结果：突破性感染后，接受mRNA疫苗治疗的儿童表现出增强的Spike肽特异性Th1应答.此外,它们的Spike特异性T细胞表现出独特的CD4+IFN-γ+IL10+细胞富集，类似于具有混合免疫的成年人的特征。重要的是,疫苗接种不会阻碍靶向膜的多特异性T细胞反应的发展，核蛋白,和ORF3a/7/8抗原。
结论：儿童，先前使用基于Spike的mRNA疫苗并经历有症状或无症状的突破性感染，保留了增强和多样化Th1/IL-10抗原特异性T细胞对多种SARS-CoV-2蛋白的反应的能力。这些发现反映了与成人混合细胞免疫相关的特征，已知赋予对严重COVID-19的抗性。
背景：本研究由新加坡国家医学研究委员会（NMRC）资助（COVID19RF-0019，MOH-000019，MOH-000535，OFLCG19May-0034和MOH-OFYIRG19nov-0002）。
