Bartsch Yannic C, St Denis Kerri J, Kaplonek Paulina, Kang Jaewon, Lam Evan C, Burns Madeleine D, Farkas Eva J, Davis Jameson P, Boribong Brittany P, Edlow Andrea G, Fasano Alessio, Shreffler Wayne, Zavadska Dace, Johnson Marina, Goldblatt David, Balazs Alejandro B, Yonker Lael M, Alter Galit
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Massachusetts General Hospital Department of Pediatrics, Mucosal Immunology and Biology Research Center, Boston, MA, USA.
bioRxiv. 2022 Jan 4:2021.10.07.463592. doi: 10.1101/2021.10.07.463592.
While children have been largely spared from COVID-19 disease, the emergence of viral variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Given the recent announcement of incomplete immunity induced by the pediatric dose of the BNT162b2 vaccine in young children, here we aimed to deeply profile and compare the vaccine-induced humoral immune response in 6-11 year old children receiving the pediatric (50μg) or adult (100μg) dose of the mRNA-1273 vaccine compared to adults and naturally infected children or children that experienced multi inflammatory syndrome in children (MIS-C) for the first time. Children elicited an IgG dominant vaccine induced immune response, surpassing adults at a matched 100μg dose, but more variable immunity at a 50μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron receptor binding domain-binding, but robustly preserved omicron Spike-receptor binding, with robustly preserved Fc-receptor binding capabilities, in a dose dependent manner. These data indicate that while both 50μg and 100μg of mRNA vaccination in children elicits robust cross-VOC antibody responses, 100ug of mRNA in children results in highly preserved omicron-specific functional humoral immunity.
虽然儿童在很大程度上未受新冠病毒病的影响，但具有更高传播性的关注变异株（VOC）的出现，再加上口罩强制令的波动以及学校重新开放，导致儿童感染和患病情况增加。因此，迫切需要为所有年龄段的儿童接种新冠疫苗。然而，儿童对mRNA疫苗的反应是否与成人相同，以及剂量是否能引发最佳免疫反应仍不清楚。鉴于最近宣布的幼儿接种BNT162b2疫苗儿科剂量诱导的免疫不完全，我们旨在深入分析和比较6至11岁儿童接种儿科（50μg）或成人（100μg）剂量的mRNA-1273疫苗后的疫苗诱导体液免疫反应，并与成人、自然感染儿童或首次发生儿童多系统炎症综合征（MIS-C）的儿童进行比较。儿童产生了以IgG为主的疫苗诱导免疫反应，在100μg匹配剂量下超过成人，但在50μg剂量下免疫反应更具变异性。无论滴度如何，儿童产生的抗体具有增强的Fc受体结合能力。此外，与成人一样，儿童产生了跨VOC体液免疫，其特征是奥密克戎受体结合域结合下降，但奥密克戎刺突蛋白-受体结合能力强劲保留，且Fc受体结合能力也以剂量依赖方式强劲保留。这些数据表明，虽然儿童接种50μg和100μg的mRNA疫苗均能引发强劲的跨VOC抗体反应，但儿童接种100μg的mRNA可产生高度保留的奥密克戎特异性功能性体液免疫。
