{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:04:53Z","timestamp":1784293493163,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic allergic reactions (sARs) after vaccination are life\u2010threatening and can erode vaccine confidence. Distinguishing sARs from immunization stress\u2010related responses (ISRRs), which require different management, remains a clinical challenge. We sought to identify biomarkers distinguishing sARs from ISRRs, characterize their early immune and metabolic pathways, and determine whether immediate reactions alter subsequent vaccine\u2010induced immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We profiled samples from a double\u2010blind, placebo\u2010controlled BNT162b2 re\u2010vaccination trial (NCT04977479) in individuals with allergic reactions to a first mRNA vaccine dose. Whole\u2010blood transcriptomics, plasma proteomics and metabolomics, blood counts, and flow cytometry were assessed 0.5\u201324\u2009h after the second dose, booster, and placebo. Anti\u2010spike antibodies were measured longitudinally; anti\u2010nucleocapsid antibodies identified intercurrent infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Interferon and antiviral transcriptional programs 24\u2009h post\u2010vaccination and subsequent anti\u2010spike antibody responses were preserved across reaction groups. However, longer\u2010than\u2010recommended intervals between first and second doses were associated with lower antibody titers. In participants with mild to no reactions, neutrophil activation and degranulation signatures peaked at 6\u2009h; these responses were blunted in ISRRs despite comparable early neutrophil mobilization. ISRRs were also marked by a stress\u2010metabolic state with early norepinephrine increases; sustained bisphosphoglycerate and 2\/3\u2010phosphoglycerate elevations; reduced basophil activation\/recruitment markers (CD63, CD193); downregulation of basophil\u2010associated transcripts (CPA3, HDC, MS4A3); and upregulation of stress\u2010linked genes (OTOF, SNORD3). sARs showed opposite metabolic trajectories and trended toward early neutrophil CD63 upregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Time\u2010resolved immune and metabolic signatures identified candidate biomarkers distinguishing ISRRs from sARs, with implications for diagnosis, management, and vaccine adherence. Notably, reactions did not impair vaccine\u2010elicited antiviral responses or humoral immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70442","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:34:17Z","timestamp":1784291657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time\u2010Resolved Multi\u2010Omics Identify Biomarkers of Immediate Reactions to\n                    <scp>mRNA<\/scp>\n                    Vaccination"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0128-5461","authenticated-orcid":false,"given":"Ana","family":"Olivera","sequence":"first","affiliation":[{"name":"Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)  Bethesda Maryland 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