Document Type
Article
Publication Date
2-23-2026
Original Citation
Eryilmaz G,
Yazici Y,
Marches R,
Mimitou E,
Kenyon-Pesce L,
Handrejk K,
Jangra S,
Schotsaert M,
García-Sastre A,
Kuchel G,
Banchereau J,
Ucar D.
Dose-dependent IFN programs in myeloid cells after mRNA and adenovirus COVID-19 vaccination. JCI Insight. 2026;11(4):e199245.
Keywords
JGM, SS1, Humans, COVID-19, Myeloid Cells, COVID-19 Vaccines, SARS-CoV-2, Adult, Interferons, Female, Male, BNT162 Vaccine, Vaccination, Antibodies, Viral, 2019-nCoV Vaccine mRNA-1273, Middle Aged, RNA, Messenger, Longitudinal Studies
JAX Source
JCI Insight. 2026;11(4):e199245.
ISSN
2379-3708
PMID
41729080
DOI
https://doi.org/10.1172/jci.insight.199245
Grant
NIH grant R01 AI142086 (to DU, JB, and GK), U19 AI135972 (to AGS), U01 AI165452 (to DU, AGS, and GK), R01 AI160706 (to MS), and P30 AG067988 (to GK).
Abstract
BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and its target genes (e.g., MX1, MX2, DDX58), with transcriptional and epigenetic profiles distinct from the robust IFN program observed after mRNA boosting or a single Ad26.COV2.S dose (ISG-high). In vitro stimulation of human monocytes showed that IFN-α alone recapitulates ISG-dim, whereas both IFN-α and IFN-γ are required for ISG-high.CONCLUSIONThese findings define dose-dependent IFN programming in human myeloid cells and highlight mechanistic differences between priming and boosting, with implications for optimizing vaccine platform choice, dose scheduling, and formulation.FUNDINGNIH grants AI142086, U19 AI135972, U01 AI165452, U01 AI165452, R01 AI160706, and P30 AG067988.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.