ArticleNPJ vaccines2025
Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport.
Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Assessing the Risk of Myocarditis Post-COVID-19 Vaccination: A Systematic Review of Case Reports from 2023 to 2025.Cardiovascular toxicology · 2026Pooled it
- mRNA Therapeutics Beyond Infectious Diseases: Expanding Therapeutic Applications and Future Perspectives.Immunity, inflammation and disease · 2026Review
- mRNA Vaccines for Influenza: Hope for a Universal Vaccine?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- mRNA vaccines for HBV: Mechanisms, preclinical advances, and therapeutic clinical progress.Molecular therapy. Nucleic acids · 2026Review
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Eliciting antitumor immunity via therapeutic cancer vaccines.Cellular & molecular immunology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
Self-amplifying RNA (saRNA)-based vaccines have emerged as a potent and durable RNA vaccine platform relative to first generation mRNA vaccines. However, RNA vaccine platforms trigger undesirable side effects at protective doses, underscoring the need for improved tolerability. To address this, we leveraged the Cardiovirus leader protein, which is well-characterized to dampen host innate signaling by modulating nucleocytoplasmic transport (NCT). Co-administration of a leader-protein-encoding mRNA (which we have named "RNAx") delivered alongside vaccine cargo saRNA reduced interferon production while enhancing Influenza hemagglutinin (HA) expression in human primary cells and murine models. RNAx potently decreased serum biomarkers of reactogenicity after immunizations with an HA-expressing saRNA-LNP vaccine while maintaining the magnitude of the antibody and cellular response. RNAx also consistently enhanced binding antibody titers after a single injection and in some conditions enhanced binding antibody and neutralization titers post-boost. These findings support RNAx as a promising platform approach for improving tolerability of saRNA-LNP vaccines while preserving or enhancing immunogenicity.
Identifiers
What OpenQuestion holds
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.