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The cellular and molecular mechanisms driving variable vaccine-induced immune responses remain underexplored, limiting comprehensive vaccine evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using single-cell sequencing, we profiled and compared cellular dynamic, transcriptomic profiles, the immune repertoire, and cellular communication in vaccine recipients with high and low antibody titers after Ad5-nCoV booster vaccination, using peripheral blood mononuclear cell samples collected from a cohort of 144 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cellular profiling revealed no significant changes in most immune cell subsets. However, high responders exhibited increased cytotoxic CD8+ lymphocytes and natural killer T cells, with reduced CD8+ mucosal-associated invariant T cells. This group showed up-regulated immune and effector genes, down-regulated proinflammatory genes, and elevated inhibitory gene expression in clonal natural killer cells, accompanied by enhanced CD8+ T-cell clonal expansion. In addition, the variable and joining (VJ) gene usage of B and T cells in the high-response group showed biased patterns, with preferential expression of IGLJ3, IGKJ3, IGHV3-33, and IGHJ4 in B cells and TRAV27, TRAJ33, TRBV9, and TRBJ2-7 in T cells. Cell communication also indicated balanced proinflammatory and anti-inflammatory cytokine expression in high responders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings elucidate the cellular and molecular mechanisms underlying robust immune responses to the Ad5-nCoV booster, highlighting the critical role of cellular immunity. By integrating humoral and cellular insights, this study offers a new perspective of comprehensive framework for evaluating vaccine efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag078","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:33:41Z","timestamp":1770122021000},"page":"1046-1057","source":"Crossref","is-referenced-by-count":0,"title":["Single-Cell Sequencing Reveals Varying Cell-Mediated Immunity Profiles in Individuals With Distinct Antibody Responses Following Ad5-nCoV Booster"],"prefix":"10.1093","volume":"233","author":[{"given":"Conghui","family":"Liao","sequence":"first","affiliation":[{"name":"School of Public Health, Sun Yat-Sen University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2250-8528","authenticated-orcid":false,"given":"Yan","family":"Long","sequence":"additional","affiliation":[{"name":"School of Public 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Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahai","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Public Health, Sun Yat-Sen University , Guangzhou ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products , Guangzhou ,","place":["China"]},{"name":"Institute of One Health, Wenzhou Medical University , Wenzhou, Zhejiang ,","place":["China"]},{"name":"Hainan Key Novel Thinktank, \u201cOne Health\u201d Research Center, Hainan Medical University , Haikou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunfu","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou ,","place":["China"]},{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University , 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