Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore.
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
Nat Med. 2024 May;30(5):1373-1383. doi: 10.1038/s41591-024-02962-3. Epub 2024 Apr 30.
The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5-12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children.
关于疫苗诱导免疫反应持久性的信息匮乏，以及保护相关性的不确定性，阻碍了针对新出生队列的基于证据的 COVID-19 疫苗接种政策的制定。在这里，为了弥补这些知识空白，我们对接受 BNT162b2 疫苗接种的 5-12 岁健康儿童进行了一项队列研究。我们在 1 年内连续测量了结合抗体和中和抗体滴度（nAb）、针对刺突的记忆 B 细胞（MBC）和刺突反应性 T 细胞反应。我们发现，儿童在接受两剂 BNT162b2 后会产生抗体、MBC 和 T 细胞反应，且接种后 6 个月的抗体和 T 细胞反应高于成年人。加强针（第三针）仅提高了抗体滴度，而对 MBC 和 T 细胞反应没有影响。在具有混合免疫的儿童中，在两剂疫苗接种后感染的儿童中，nAb 和 T 细胞反应最高。结合 IgG 滴度、MBC 和 T 细胞反应具有预测性，T 细胞是在混合免疫之前预防有症状感染的最重要预测因子；nAb 仅与混合免疫后保护相关。MBC 和 T 细胞反应随时间的稳定表明，即使 nAb 减弱，也能持续预防有症状的 SARS-CoV-2 感染。加强针接种不会为健康儿童提供额外的免疫保护。
