Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2026

Alphavirus RNA capping dynamics and their impact on self-amplifying RNA vaccines (#151)

Yewen YW Wong 1 , Dahai DL Luo 1
  1. NTU, Singapore, SINGAPORE

Alphaviruses are positive‑sense RNA viruses that synthesise and cap their genomes through the viral replication complex. Despite the crucial roles of the RNA cap for translation and immune evasion, work from the Sokoloski lab has shown that alphavirus capping is not completely efficient. Early in infection, twice as much noncapped RNA than capped RNA is produced, and this ratio only approaches parity during late infection. This pattern suggests that capping efficiency may be deliberately constrained, potentially serving as a self‑regulatory mechanism to balance replication, immune recognition, and pathogenicity. To explore this, we aim to improve the efficiency of alphavirus capping through structure-guided mutagenesis of nsP1, the viral capping enzyme, within trans replicon systems. Beyond fundamental insights into alphavirus replication biology, this work has translational relevance: self‑amplifying RNA vaccine platforms are derived from alphavirus replicons, and their performance may be shaped by capping. Understanding how modulation of capping efficiency impacts replication dynamics and RNA immunogenicity could inform the rational design of next‑generation self‑amplifying RNA vaccines.

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