{"doi":"10.1101/2025.08.15.668720","title":"Dose-dependent interferon programs in myeloid cells after mRNA and adenovirus COVID-19 vaccination","abstract":"Abstract The 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 three FDA-approved COVID-19 vaccines at single-cell multi-omic resolution. We longitudinally profiled SARS-CoV-2–naïve adults (n=31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multi-omic data (DOGMA-seq). We discovered a distinct, transient interferon program (ISG-dim) that emerged specifically 1-2 days after the first mRNA dose in ∼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 interferon 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. These findings define dose-dependent interferon programming in human myeloid cells, highlight mechanistic differences between priming and boosting, with implications for optimizing vaccine platform choice, dose scheduling, and formulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572645,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1479608,"name":"Yilmaz Yucehan Yazici","orcid":null,"position":1,"is_corresponding":false},{"id":229305,"name":"Radu Marcheş","orcid":null,"position":2,"is_corresponding":false},{"id":36092,"name":"Eleni P. Mimitou","orcid":"0000-0001-9737-6394","position":3,"is_corresponding":false},{"id":1167329,"name":"Lisa Kenyon‐Pesce","orcid":null,"position":4,"is_corresponding":false},{"id":1479609,"name":"Kim Handrjek","orcid":null,"position":5,"is_corresponding":false},{"id":555491,"name":"Sonia Jangra","orcid":"0000-0002-5671-1632","position":6,"is_corresponding":false},{"id":107923,"name":"Michael Schotsaert","orcid":"0000-0003-3156-3132","position":7,"is_corresponding":false},{"id":1489,"name":"Adolfo Garcı́a-Sastre","orcid":"0000-0002-6551-1827","position":8,"is_corresponding":false},{"id":225893,"name":"George A. Kuchel","orcid":"0000-0001-8387-7040","position":9,"is_corresponding":false},{"id":55820,"name":"Jacques Banchereau","orcid":"0000-0003-3535-7221","position":10,"is_corresponding":false},{"id":42663,"name":"Duygu Ucar","orcid":"0000-0002-9772-3066","position":11,"is_corresponding":false},{"id":1173796,"name":"Giray Naim Eryilmaz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40894688","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}