Cohen Carolyn A, Grzelak Ludivine, Chiu Susan S, Hui David Sc, Kwan Mike Yw, Tsang Owen Ty, Chan Wai Hung, Yau Yat Sun, Lee Kelly Wk, Mori Masashi, Amarasinghe Gaya K, Cheng Samuel Ms, Poon Leo Lm, Peiris Malik, Valkenburg Sophie A
HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Nat Commun. 2025 Aug 23;16(1):7879. doi: 10.1038/s41467-025-63263-y.
As intrinsic differences in humoral immune response to SARS-CoV-2 between children and adults remain unclear, we improved characterisation by defining the kinetics, specificity and function of antibodies to SARS-CoV-2 in children (n = 146, aged 9.4 ± 4.8 years with n = 257 samples) compared to adults (n = 85, aged 39.5 ± 15.2 years with n = 122 samples). We used plasma samples from an infection and vaccination-naive cohort study with RT-PCR confirmed ancestral B.1* SARS-CoV-2 virus infection with asymptomatic or mild disease, collected in Hong Kong between March to December 2020, from acute (0-14 days post infection) to convalescent (15-206 days) timepoints. Children had significantly lower primary antibody responses against SARS-CoV-2 proteins overall, leading to a less isotype switched response. While children had lower OC43 Spike and SARS-CoV-2 S2 IgG and avidity than adults, they exhibited higher avidities for SARS-CoV-2 whole Spike and Nucleocapsid, and higher levels of Spike FcγR-binding antibodies. Adults' SARS-CoV-2 antibody responses could be derived from high avidity pre-existing cross-reactive common cold coronavirus B cell responses, whilst children appear to generate a de novo SARS-CoV-2- specific Spike and Nucleocapsid IgG with robust Fc receptor (FcR) binding ability and high avidity at a higher proportion than adults, thus their responses are more targeted and functional for SARS-CoV-2.
由于儿童和成人对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的体液免疫反应的内在差异尚不清楚，我们通过定义儿童（n = 146，年龄9.4±4.8岁，共257份样本）与成人（n = 85，年龄39.5±15.2岁，共122份样本）体内针对SARS-CoV-2抗体的动力学、特异性和功能，改进了特征描述。我们使用了来自一项未感染和未接种疫苗队列研究的血浆样本，该研究通过逆转录聚合酶链反应（RT-PCR）确认感染了原始B.1*SARS-CoV-2病毒，且为无症状或轻症疾病，样本于2020年3月至12月在香港采集，涵盖从急性期（感染后0 - 14天）到恢复期（15 - 206天）的时间点。总体而言，儿童针对SARS-CoV-2蛋白的初次抗体反应显著较低，导致同种型转换反应较少。虽然儿童针对OC43刺突蛋白和SARS-CoV-2 S2的IgG及亲和力低于成人，但他们对SARS-CoV-2全刺突蛋白和核衣壳的亲和力更高，且刺突蛋白FcγR结合抗体水平更高。成人的SARS-CoV-2抗体反应可能源自高亲和力的预先存在的交叉反应性普通感冒冠状病毒B细胞反应，而儿童似乎以比成人更高的比例产生具有强大Fc受体（FcR）结合能力和高亲和力的全新SARS-CoV-2特异性刺突蛋白和核衣壳IgG，因此他们的反应对SARS-CoV-2更具针对性且功能性更强。
