# Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity

Article · Sanchez-David RY, Nemegeer J, Le HD, Žusinaite E, Spiga L, Gonçalves A, Tregoning JS, Merits A, Maillard PV

- Archive id: doi:10.1038/s41467-026-77816-2
- Published: 2026-09-28
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-026-77816-2
- PMID: 42805992
- PMCID: PMC13620136
- Citations: 0
- Source URL: https://doi.org/10.1038/s41467-026-77816-2
- PDF: https://europepmc.org/articles/PMC13620136/pdf
- Provenance: europepmc

## Abstract

Self-amplifying RNA (saRNA) offers a powerful approach for vaccine development, as its replicative nature within cells provides prolonged antigen expression together with self-adjuvanticity. However, its potency is often limited by innate immune responses, particularly those triggered by intracellular double-stranded RNA (dsRNA), highlighting the need for strategies that can boost saRNA efficacy without compromising its immunostimulatory properties. Here we show that the cis-expression of the Nodamura virus (NoV) B2 protein markedly enhances saRNA-driven transgene expression by alleviating key cell-intrinsic antiviral effectors. In stem cells, NoV B2 limits the accumulation of Dicer-generated viral small RNAs, consistent with suppression of antiviral RNA interference, while in somatic cells, it prevents protein kinase R (PKR)-driven translational shutdown. NoV B2 sequesters dsRNA at the cell periphery, shielding it from antiviral effectors without suppressing type I interferon induction or signalling, thereby preserving saRNA's immunostimulatory properties, while enhancing its transgene expression potential. These findings reveal a strategy to overcome intracellular antiviral restriction of saRNA while preserving adjuvanticity, with implications for the design of more effective saRNA-based vaccines and therapeutics.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

Cited in dossiers:
- [mRNA Therapeutics & Cancer Vaccines: State of the Field (October 2026)](https://space-kitty.com/dossiers/mrna-cancer-vaccines)

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