{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:47Z","timestamp":1792785947847,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Major Research Plan Cultivation"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92369117"],"award-info":[{"award-number":["92369117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92269205"],"award-info":[{"award-number":["92269205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nanjing Medical Key Science and Technology Development Project","award":["ZKX22028"],"award-info":[{"award-number":["ZKX22028"]}]},{"name":"Clinical Trials from the Nanjing Drum Tower Hospital","id":[{"id":"https:\/\/ror.org\/026axqv54","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Hospital of Medical School"},{"DOI":"10.13039\/501100008048","name":"Nanjing University","doi-asserted-by":"publisher","award":["2022-LCYJ-MS-08"],"award-info":[{"award-number":["2022-LCYJ-MS-08"]}],"id":[{"id":"10.13039\/501100008048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>With the viral variants and waning of vaccine-induced immunity over time, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections have become the next challenge following the coronavirus disease 2019 pandemic, highlighting the need for broader and sustained immune responses. As the first defense against viral invasion, mucosal immunity is inducible by SARS-CoV-2 infection. Previous studies focused on serum antibodies and cellular immunity in those with acquired immunity, but the specific role of mucosal immunity in breakthrough infection remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single-cell RNA sequencing (scRNA-seq) on nasal swabs and peripheral blood mononuclear cells from a prospective cohort of breakthrough-infected individuals. Findings were validated with flow cytometry and enzyme-linked immunosorbent assay in a separate multicenter cohort. In vitro experiments using recombinant protein were conducted on the human monocytic leukemia cell line THP-1, as effector cells, to investigate underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mucosal neutrophils showed the most significant dynamic changes in after infection. A unique subpopulation of high\u2013BPI fold-containing family A member 1 (BPIFA1)\u2013expressing (BPI+) neutrophils was identified and found to be positively correlated with neutralizing antibody and immunoglobulin G levels in the breakthrough patient (Pt) group. With scRNA-seq, cell communication analysis revealed enhanced interactions between BPI+ neutrophils and macrophages. In vitro, BPIFA1 stimulation activated the nuclear factor (NF)\u2013\u03baB pathway in THP-1 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BPI+ neutrophils in the respiratory mucosa are pivotal in driving immune responses during breakthrough infection in those with acquired immunity by modulating macrophage activity via the NF-\u03baB pathway line. It may trigger the production of interleukin 6, the immunostimulatory phenotype necessary for B-cell engagement, to complete the innate-to-adaptive immunity relay, which highlights their potential as a target for novel mucosal vaccine strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag267","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:02:20Z","timestamp":1778760140000},"page":"583-593","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Mucosal BPI fold-containing family A member 1-High-Expressing Neutrophils and their Immune Defense roles in Severe Acute Respiratory Syndrome Coronavirus 2 Breakthrough Infection via single-cell RNA sequencing"],"prefix":"10.1093","volume":"234","author":[{"given":"Xue","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiu","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology, Affiliated Hospital of Hangzhou Normal University , Hangzhou, Zhejiang 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