Evidence map›Paper›PMID 40733695›Full record

ArticleVaccines2025

Pre-Vaccination Immune Profiles and Responsiveness to Innate Stimuli Predict Reactogenicity and Antibody Magnitude Following mRNA Vaccination.

Amanda E Zelkoski, Emilie Goguet, Emily Samuels Darcey, Mohamad-Gabriel Alameh, Hooda Said, Simon Pollett, John H Powers, Eric D Laing, Cara Olsen, Edward Mitre and 1 more

Abstract read
In one paragraph

Article in Vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Single-cell RNA sequencing offers novel perspectives in viral infection research.Frontiers in cellular and infection microbiology · 2026
    Pooled it
  2. Review
  3. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Amanda E ZelkoskiDepartment of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.
Emilie GoguetThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA.ORCID 0000-0001-6284-4346
Emily Samuels DarceyThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA.
Mohamad-Gabriel AlamehDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-5672-6930
Hooda SaidDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Simon PollettThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20814, USA.
John H PowersClinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.ORCID 0000-0002-5150-5119
Eric D LaingDepartment of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.ORCID 0000-0002-5574-2584
Cara OlsenDepartment of Preventive Medicine & Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Edward MitreDepartment of Microbiology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.ORCID 0000-0001-7506-3266
Allison M W MalloyDepartment of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.ORCID 0000-0003-2962-0302

Funding

Defense Health Agency HU00012120104Defense Health Program HU00012020067Defense Health Program HU00012120094National Institute of Allergy and Infectious Diseases HU00011920111
6 · The paper itself

Abstract

backgroundWhile 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.

methodsWe 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.

resultsBaseline 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.

conclusionsThe 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.

Indexed as

antibodyBNT162b2correlatesdendritic cellsinnate immune responsemonocytesmRNA vaccinepredictorsreactogenicity

Identifiers

PMID40733695
PMCPMC12298116

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.