{"entity": "publication", "iuid": "39cafd188c9e4072bfd89e2955794ce5", "timestamp": "2026-08-12T06:14:23.088Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/39cafd188c9e4072bfd89e2955794ce5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/39cafd188c9e4072bfd89e2955794ce5"}}, "title": "Immunogenicity and innate immunity to high-dose and repeated vaccination of modified mRNA versus unmodified mRNA.", "authors": [{"family": "Engstrand", "given": "Olivia", "initials": "O"}, {"family": "Joas", "given": "Gustav", "initials": "G"}, {"family": "Miranda", "given": "Marcos C", "initials": "MC"}, {"family": "Yan", "given": "Xianglei", "initials": "X"}, {"family": "Lenart", "given": "Klara", "initials": "K"}, {"family": "Cerveira", "given": "Rodrigo Arcoverde", "initials": "RA"}, {"family": "Reinhardt", "given": "Annika", "initials": "A"}, {"family": "Lor\u00e9", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2025-09-09", "journal": {"title": "Mol Ther Nucleic Acids", "issn": "2162-2531", "volume": "36", "issue": "3", "pages": "102588", "issn-l": "2162-2531"}, "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 \u03bcg) and modified (400 \u03bcg and 800 \u03bcg) 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-\u03b1 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.", "doi": "10.1016/j.omtn.2025.102588", "pmid": "40612710", "labels": {"Affinity Proteomics Stockholm": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12221724"}, {"db": "pii", "key": "S2162-2531(25)00142-8"}], "notes": [], "created": "2025-09-19T14:41:12.463Z", "modified": "2025-11-28T14:59:07.787Z"}