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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.<\/jats:p>","DOI":"10.3390\/vaccines13030262","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T04:10:42Z","timestamp":1740975042000},"page":"262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Hidden Guardian: The Stability and Spectrum of Antibody-Dependent Cell-Mediated Cytotoxicity in COVID-19 Response in Chinese Adults"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5819-8803","authenticated-orcid":false,"given":"Jinge","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengze","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlian","family":"Li","sequence":"additional","affiliation":[{"name":"Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, 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University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-372X","authenticated-orcid":false,"given":"Xionglin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","unstructured":"(2025, January 23). 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