{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:30:31Z","timestamp":1786559431811,"version":"build-2736575974"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"862","funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NIHR-CS-2016-16-011"],"award-info":[{"award-number":["NIHR-CS-2016-16-011"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:p>\n                    Adults who survive intensive care unit (ICU) admission with sepsis (sepsis survivors) have immune impairments involving concurrent inflammation and immunosuppression that increase their long-term risk of reinfections and mortality. Vaccine immunogenicity could therefore be abnormal in sepsis survivors but has never been examined. Here, in a 1:1 randomized, placebo-controlled trial, we tested the efficacy and immunogenicity of a single intramuscular dose of 13-valent pneumococcal conjugate vaccine (PCV13) in 214 sepsis survivors at ICU discharge. The PCV13 group (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a0104) experienced 43 primary outcome events (time to first infection-related rehospitalization or death during 365 days of follow-up) among 72.5 person-years of follow-up compared with 38 events among 76.5 person-years of follow-up in the placebo group (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a0110) [hazard ratio, 1.23 (95% CI, 0.80 to 1.91)]. The PCV13 group experienced higher rates of reinfections and received earlier antibiotic prescriptions in primary care. There were no vaccine-related serious adverse events. PCV13 immunogenicity assessments included serotype-specific immunoglobulin G (IgG), immunophenotyping, and pan-leukocyte RNA sequencing measured at baseline and 10 and 30 days postrandomization. PCV13-induced serotype-specific IgG responses varied across serotypes and participants, without excessive cytokine responses. PCV-induced blood transcriptional module responses in antigen-presenting cells and helper T cells were also variable. Variations in PCV13 immunogenicity were associated with age in men, body mass index in women, and cytotoxicity-associated gene modules regardless of sex. This trial showed that PCV13 administered at ICU discharge did not benefit this sepsis survivor population and underscores the need for further research to delineate treatable molecular mechanisms of postsepsis immune dysfunction (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03565159\">NCT03565159<\/jats:ext-link>\n                    ).\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aeb4113","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:58:18Z","timestamp":1786557498000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccination to accelerate immune recovery after sepsis"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-2538","authenticated-orcid":true,"given":"Manu","family":"Shankar-Hari","sequence":"first","affiliation":[{"name":"Peter Gorer Department of Immunobiology, School of Immunology &amp; Microbial Sciences, King\u2019s College London, London, UK."},{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, Scotland, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-7361","authenticated-orcid":true,"given":"Peter","family":"Smith","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, Scotland, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-8844","authenticated-orcid":true,"given":"Tamas","family":"Szakmany","sequence":"additional","affiliation":[{"name":"Critical Care Directorate, Aneurin Bevan University Health Board, Newport, Wales, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-2873","authenticated-orcid":true,"given":"Charlotte","family":"Summers","sequence":"additional","affiliation":[{"name":"Victor Phillip Dahdaleh Heart &amp; Lung Research Institute, University of Cambridge, Cambridge, UK."},{"name":"Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5766-990X","authenticated-orcid":true,"given":"Peter J.","family":"McGuigan","sequence":"additional","affiliation":[{"name":"Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK."},{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen\u2019s University Belfast, Belfast, Northern Ireland, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brealey","sequence":"additional","affiliation":[{"name":"NIHR University College London Hospitals Biomedical Research Centre, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-8391","authenticated-orcid":true,"given":"Phil","family":"Hopkins","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospital NHS Foundation Trust, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-1232","authenticated-orcid":true,"given":"Ben","family":"Creagh Brown","sequence":"additional","affiliation":[{"name":"Royal Surrey NHS Foundation Trust and School of Medicine, University of Surrey, Guildford, 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