Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
EBioMedicine. 2024 Jul;105:105203. doi: 10.1016/j.ebiom.2024.105203. Epub 2024 Jun 18.
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.
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.
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.
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.
This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
尽管接种疫苗的儿童突破性感染率不断上升，但对于由疫苗接种和自然感染产生的 SARS-CoV-2 混合免疫，儿科人群中的了解仍不够充分。
我们进行了一项前瞻性纵向研究，以调查在接种 mRNA 疫苗的 5-11 岁儿童队列中，突破性 SARS-CoV-2 感染引起的抗原特异性 T 细胞反应的幅度、特异性和细胞因子谱。该纵向分析涉及接种疫苗后 16 个月的六个不同时间点，在此期间共分析了 159 份血样。所有至少随访 12 个月的儿童（n=26）均经历了突破性感染。我们使用最小量的血液样本进行细胞因子释放测定，并通过细胞内细胞因子染色验证这些反应的细胞来源。
突破性感染后，接受 mRNA 疫苗接种的儿童表现出针对 Spike 肽的增强的 Th1 反应。此外，他们的 Spike 特异性 T 细胞表现出独特的 CD4+ IFN-γ+IL10+细胞富集，这一特征类似于具有混合免疫的成年人。重要的是，疫苗接种并未阻碍针对膜、核蛋白和 ORF3a/7/8 抗原的多特异性 T 细胞反应的发展。
先前接受基于 Spike 的 mRNA 疫苗接种并经历有症状或无症状突破性感染的儿童能够增强和多样化针对多种 SARS-CoV-2 蛋白的 Th1/IL-10 抗原特异性 T 细胞反应。这些发现与成年人中与混合细胞免疫相关的特征相吻合，已知混合细胞免疫可抵抗严重的 COVID-19。
这项研究由新加坡国家医学研究理事会（NMRC）资助（COVID19RF-0019、MOH-000019、MOH-000535、OFLCG19May-0034 和 MOH-OFYIRG19nov-0002）。
