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<p>mRNA-lipid nanoparticle (LNP) vaccines induce robust adaptive immune responses and have proven highly effective against SARS-CoV-2. However, their long-term effectiveness is limited by waning humoral responses, which decline substantially within the first six months post-boost vaccination. DNA-LNPs are being investigated as an alternative vaccine platform, offering prolonged antigen expression and robust immunity. Here, we compare DNA- and mRNA-LNP vaccines encoding CD40L-adjuvanted SARS-CoV-2 XBB.1.5 Spike (S<sub>XBB.1.5</sub>-CD40L) in a long-term in vivo challenge model. Both nucleic acid vaccines induced strong neutralizing antibody responses and conferred equivalent protection in Syrian hamsters challenged three weeks post-boost. Notably, DNA-LNP vaccination maintained high binding and neutralizing antibody titers six months post-boost, whereas mRNA-LNPs exhibited a marked decline. Correspondingly, while S<sub>XBB.1.5</sub>-CD40L DNA-LNP vaccination completely protected from weight loss, viral replication, and lung pathology at this late timepoint, S<sub>XBB.1.5</sub>-CD40L mRNA-LNP vaccination conferred minimal protection. These findings demonstrate that DNA-LNPs can sustain durable immunity, highlighting their potential as a next-generation vaccine platform that could reduce the need for frequent boosters.</p>

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Durability of DNA-LNP and mRNA-LNP vaccine-induced immunity against SARS-CoV-2 XBB.1.5

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月31日

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  • Levi Tamming,
  • Casey Lansdell,
  • Wanyue Zhang,
  • Diana Duque,
  • Jegarubee Bavananthasivam,
  • Grant Frahm,
  • Annabelle Pfeifle,
  • Sathya N. Thulasi Raman,
  • Jianguo Wu,
  • Caroline Gravel,
  • Andrew Stalker,
  • Matthew Stuible,
  • Yves Durocher,
  • Wangxue Chen,
  • Lisheng Wang,
  • Simon Sauve,
  • Anh Tran,
  • Michael J. W. Johnston,
  • Xuguang Li

摘要

mRNA-lipid nanoparticle (LNP) vaccines induce robust adaptive immune responses and have proven highly effective against SARS-CoV-2. However, their long-term effectiveness is limited by waning humoral responses, which decline substantially within the first six months post-boost vaccination. DNA-LNPs are being investigated as an alternative vaccine platform, offering prolonged antigen expression and robust immunity. Here, we compare DNA- and mRNA-LNP vaccines encoding CD40L-adjuvanted SARS-CoV-2 XBB.1.5 Spike (SXBB.1.5-CD40L) in a long-term in vivo challenge model. Both nucleic acid vaccines induced strong neutralizing antibody responses and conferred equivalent protection in Syrian hamsters challenged three weeks post-boost. Notably, DNA-LNP vaccination maintained high binding and neutralizing antibody titers six months post-boost, whereas mRNA-LNPs exhibited a marked decline. Correspondingly, while SXBB.1.5-CD40L DNA-LNP vaccination completely protected from weight loss, viral replication, and lung pathology at this late timepoint, SXBB.1.5-CD40L mRNA-LNP vaccination conferred minimal protection. These findings demonstrate that DNA-LNPs can sustain durable immunity, highlighting their potential as a next-generation vaccine platform that could reduce the need for frequent boosters.