{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:16:06Z","timestamp":1792790166213,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pediatrics RAMP","award":["HU00012020067"],"award-info":[{"award-number":["HU00012020067"]}]},{"name":"Department of Pediatrics RAMP","award":["HU00012120094"],"award-info":[{"award-number":["HU00012120094"]}]},{"name":"Department of Pediatrics RAMP","award":["HU00012120104"],"award-info":[{"award-number":["HU00012120104"]}]},{"name":"Department of Pediatrics RAMP","award":["HU00011920111"],"award-info":[{"award-number":["HU00011920111"]}]},{"name":"Defense Health Program","award":["HU00012020067"],"award-info":[{"award-number":["HU00012020067"]}]},{"name":"Defense Health Program","award":["HU00012120094"],"award-info":[{"award-number":["HU00012120094"]}]},{"name":"Defense Health Program","award":["HU00012120104"],"award-info":[{"award-number":["HU00012120104"]}]},{"name":"Defense Health Program","award":["HU00011920111"],"award-info":[{"award-number":["HU00011920111"]}]},{"DOI":"10.13039\/100009898","name":"Immunization Healthcare Branch of the Defense Health Agency, United States Department of Defense","doi-asserted-by":"publisher","award":["HU00012020067"],"award-info":[{"award-number":["HU00012020067"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Immunization Healthcare Branch of the Defense Health Agency, United States Department of Defense","doi-asserted-by":"publisher","award":["HU00012120094"],"award-info":[{"award-number":["HU00012120094"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Immunization Healthcare Branch of the Defense Health Agency, United States Department of Defense","doi-asserted-by":"publisher","award":["HU00012120104"],"award-info":[{"award-number":["HU00012120104"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Immunization Healthcare Branch of the Defense Health Agency, United States Department of Defense","doi-asserted-by":"publisher","award":["HU00011920111"],"award-info":[{"award-number":["HU00011920111"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["HU00012020067"],"award-info":[{"award-number":["HU00012020067"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["HU00012120094"],"award-info":[{"award-number":["HU00012120094"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["HU00012120104"],"award-info":[{"award-number":["HU00012120104"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["HU00011920111"],"award-info":[{"award-number":["HU00011920111"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: While mRNA vaccines effectively limit hospitalization and severe COVID-19 disease, the precise early innate immune mechanisms associated with their efficacy and reactogenicity remain underexplored. The identification of innate immune correlates prior to vaccination could provide mechanistic insights and potentially predict responses. Methods: We developed an in vitro model to study the innate immune activation of pre-vaccination peripheral blood mononuclear cells (PBMCs) collected from participants enrolled in a well-characterized COVID-19 BioNTech\/Pfizer BNT162b2 vaccine (BNT162b2 vaccine) cohort. Pre-vaccination PBMCs were stimulated with empty lipid nanoparticle (LNP), mRNA-LNP, or Toll-like receptor (TLR) agonists. Using multiparameter spectral flow cytometry, we analyzed the baseline immune state, innate responsiveness to stimuli, and cytokine profiles of study participants. These pre-vaccination in vitro results were analyzed for correlations with post-vaccination symptoms and spike-specific IgG responses. Results: Baseline dendritic cell (DC) states inversely correlated with the magnitude of symptoms following BNT162b2 vaccination. Heightened conventional (cDC) and weaker plasmacytoid DC (pDC) responses to RNA stimuli correlated with the magnitude of an acute IgG response. IgG durability modestly correlated with a lower pDC state but higher cDC2 and monocyte baseline states and inversely correlated with TLR3 agonist responsiveness. Conclusions: The pre-vaccination assessment of innate immune function and resting states can be used to fit models potentially predictive of immunogenicity and reactogenicity to BNT162b2 vaccination. Pre-vaccination DC states may influence reactogenicity, while the response to RNA may impact antibody responses. Our data suggest that pre-vaccination assessment offers insights into the innate mechanisms driving mRNA vaccine responses and has predictive potential.<\/jats:p>","DOI":"10.3390\/vaccines13070718","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pre-Vaccination Immune Profiles and Responsiveness to Innate Stimuli Predict Reactogenicity and Antibody Magnitude Following mRNA Vaccination"],"prefix":"10.3390","volume":"13","author":[{"given":"Amanda E.","family":"Zelkoski","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6284-4346","authenticated-orcid":false,"given":"Emilie","family":"Goguet","sequence":"additional","affiliation":[{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA"},{"name":"Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Samuels Darcey","sequence":"additional","affiliation":[{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA"},{"name":"Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5672-6930","authenticated-orcid":false,"given":"Mohamad-Gabriel","family":"Alameh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular and Molecular Therapeutics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hooda","family":"Said","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular and Molecular Therapeutics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Pollett","sequence":"additional","affiliation":[{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA"},{"name":"Infectious Disease Clinical Research Program, Department of Preventive Medicine & Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5150-5119","authenticated-orcid":false,"suffix":"III","given":"John H.","family":"Powers","sequence":"additional","affiliation":[{"name":"Clinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5574-2584","authenticated-orcid":false,"given":"Eric D.","family":"Laing","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine & Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7506-3266","authenticated-orcid":false,"given":"Edward","family":"Mitre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-0302","authenticated-orcid":false,"given":"Allison M. 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