ArticleMolecular therapy. Nucleic acids2025
Immunogenicity and innate immunity to high-dose and repeated vaccination of modified mRNA versus unmodified mRNA.
Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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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.
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Who cites it
6 citing papers in PubMed.
- mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models.Nature immunology · 2026Article
- An ORFV F1L mRNA Vaccine Candidate: Preparation, Immunogenicity, and Comparison with a Commercial Live Vaccine.Animals : an open access journal from MDPI · 2026Article
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- Rewiring the immune circuit: programming tumor-draining lymph node immunity with nanotechnology.Journal of nanobiotechnology · 2026Review
- Seasonal influenza mRNA vaccine induces stronger innate and comparable or better adaptive responses than licensed inactivated vaccines.NPJ vaccines · 2026Article
- To modify or not to modify-That is still the question for some mRNA applications.Molecular therapy. Nucleic acids · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
mRNA vaccines represent a new era with several novel constructs underway. We compared the responses of high doses and multiple repetitive immunizations of a nucleoside-modified mRNA construct to a sequence-codon-optimized unmodified mRNA construct encoding the identical model antigen (HIV-1 gag). Rhesus macaques were immunized five times at 2-week intervals, with a final boost 20 weeks later. At 24 h post-vaccination, both unmodified (160 μg) and modified (400 μg and 800 μg) mRNA constructs elicited clear but transient increase of plasmacytoid dendritic cells, intermediate CD14+ CD16+ monocytes, and neutrophils along with secretion of type I interferon (IFN)-related and inflammatory cytokines. Unmodified mRNA induced higher interleukin-7 (IL-7) and IFN-α levels, whereas modified mRNA induced higher IL-6 levels. Transcriptomic profiling showed significant upregulation of genes related to type I IFN signaling, antigen presentation, and innate immune activation induced by both mRNA constructs. The high-dose modified mRNA induced a higher number of differentially expressed genes at prime, which further increased after the fifth immunization. These differences in innate immune activation nonetheless led to similar levels and kinetics of gag-specific antibody and T cell responses. These findings offer insights into the immunogenic and reactogenic potential of different mRNA vaccine modalities, guiding future vaccine and therapy development.
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Registered trials
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.