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In addition to antibodies, pathogen-specific memory T and Bcells persist in blood and tissues, but it remains unclear how their composition and spatial distribution relate to serum antibody titers, the most common correlate of vaccine-induced protection. Understanding these relationships is essential for predicting vaccine efficacy and optimizing immunization strategies. We analyzed tissues from 58 adult human organ donors vaccinated against SARS-CoV-2, including individuals with and without prior infection. Using multivariate imputation, dimensionality reduction, and correlation, regression, and causal analyses, we identified immune signatures linking memory B cell, CD4 T cell, and CD8 T cell subsets in spleen, lung, and lung-draining lymph nodes with antibody titers and neutralizing activity. Our analyses indicate that humoral immunity is driven primarily by virus-specific B cellsand CD4 T cells in lymphoid tissues rather than blood, whereas tissue-localized CD8 T cell responses, although correlated with antibody levels, develop independently. These findings demonstrate that cross-sectional immune profiling across multiple tissues recapitulates established immunological principles and reveal that serum antibody responses emerge from coordinated cellular immune responses distributed throughout the body.<\/jats:p>","DOI":"10.64898\/2026.07.23.740375","type":"posted-content","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:11:18Z","timestamp":1784938278000},"source":"Crossref","is-referenced-by-count":0,"title":["Beyond the blood: Tissue-resident immunity shapes SARS-CoV-2 vaccine antibody responses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-2519","authenticated-orcid":false,"given":"Juliane","family":"Schr\u00f6ter","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan H.","family":"van Dorp","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Davis-Porada","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York City, NY, USA"},{"name":"UCLA David Geffen School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Teijaro","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna L.","family":"Farber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York City, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072720300629000_2026.07.23.740375v1.1","doi-asserted-by":"crossref","unstructured":"Plotkin SA (2008). 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