Modulation of lipid nanoparticle-formulated plasmid DNA drives innate immune activation promoting adaptive immunity

🥈 Top 2% JournalMar 22, 2025Cell reports. Medicine

Changes in lipid nanoparticle DNA trigger immune response that supports long-term immunity

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Abstract

HA DNA-LNP induced superior antigen-specific CD8T cell responses that persisted beyond one year.

  • The DNA-LNP formulation elicited robust innate and adaptive immunity, showing similar serological potency to mRNA-LNPs and adjuvanted protein.
  • Priming with HA DNA-LNP resulted in STING-dependent activation of migratory dendritic cell subpopulations.
  • In rabbits, immune responses from HA DNA-LNP were comparable or superior to those induced by mRNA-LNPs at the same dose.
  • A SARS-CoV-2 spike-encoding DNA-LNP demonstrated protective efficacy similar to that of spike mRNA-LNPs.
  • The findings suggest a distinct priming mechanism for DNA-LNPs that differs from mRNA-LNPs and adjuvanted protein.

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