Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has highlighted their capacity to evade neutralizing antibodies, emphasizing the need to understand the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in combating these infections. Methods: This study, conducted in Qichun City, Hubei province, from December 2021 to March 2023, involved 50 healthy Chinese adults who had received two doses of inactivated vaccines and had subsequently experienced mild infections with the Omicron BA.5 variant. Blood samples from these 50 healthy Chinese adults were collected at six distinct time points: at baseline and at the 1st, 3rd, 6th, and 9th months following the third dose of the inactivated vaccine, as well as 3 months post-breakthrough infection. Their sera were analyzed to assess ADCC and neutralization effects. Results: The results indicated that the antibodies elicited by the inactivated SARS-CoV-2 vaccine targeted the spike protein, exhibiting both pre-existing neutralizing and ADCC activities against Omicron variants BA.5 and XBB.1.5. Notably, the ADCC activity demonstrated greater stability compared to that of the neutralizing effects, persisting for at least 15 months post-vaccination, and could be augmented by additional vaccine doses and breakthrough infections. The ADCC effect associated with hybrid immunity effectively targets a spectrum of prospective Omicron variants, including BA.2.86, CH.1.1, EG.5.1, and JN.1. Conclusions: In light of its stability and broad-spectrum efficacy, we recommend the use of the ADCC effect as a biomarker for assessing protective immunity and guiding the development of vaccines and monoclonal antibodies.

Background: The continuous evolution of SARS-CoV-2 necessitates the development of targeted strategies based on the immunological profiles of distinct age groups. Despite this imperative, comprehensive insights into the dynamics and broad-spectrum efficacy of neutralizing antibodies (NAbs) against emerging variants across different age groups, particularly in children, remain inadequate. Methods: Following the termination of China’s dynamic ‘zero-COVID-19’ policy in January 2023, which coincided with a widespread Omicron outbreak and numerous breakthrough infections, a longitudinal cohort study was established encompassing all age groups in Hubei, China. Follow-up assessments were conducted in March (Visit 1), June (Visit 2), and October (Visit 3) 2023. A total of 320 individuals were randomly selected and stratified into three age categories: children (<18 years, n = 80), adults (18–59 years, n = 167), and the elderly (≥60 years, n = 73). The NAbs against emerging SARS-CoV-2 variants BA.5, XBB.1.5, EG.5, and JN.1 were evaluated for each group. Trajectory modeling was employed to classify antibody trends into five categories: low-level stability, median-level stability, high-level stability, early increase, and late increase. Results: In March 2023, children exhibited significantly higher NAb levels against BA.5, XBB.1.5, EG.5, and JN.1 compared to adults and the elderly. However, these levels rapidly declined. From June to October 2023, no significant difference in NAb levels was observed between children and the other age groups. Regarding the broad-spectrum effectiveness of NAbs, the effectiveness in children was comparable to that of adults and the elderly in March 2023. However, from June to October 2023, children’s effectiveness became significantly lower than that of the other age groups. Trajectory analysis revealed that the highest proportions of high-level stability (31.3%) and median-level stability (42.5%) were observed among children. In contrast, adults and the elderly were most commonly categorized into the early increase (adult 46.7%, elderly 49.3%) and median-level stability (adult 22.1%, elderly 20.5%) categories. Conclusions: Although children initially demonstrate higher levels of NAbs, these levels decrease more rapidly than in adults and the elderly, eventually equalizing in later stages of recovery. Furthermore, the broad-spectrum effectiveness of NAbs in children is narrower than in other age groups. These findings suggest that children are at an elevated risk of infection with newly emerging variants, underscoring the urgent need to intensify focus on reinfections among children and develop tailored strategies to protect this vulnerable population.