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<p>Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4<sup>+</sup> T cell activation; however, CD8<sup>+</sup> responses are variable, and the duration of immunity and protection against variants are limited. Here we repurpose our DNA origami vaccine nanotechnology DoriVac to target infectious viruses, namely, SARS-CoV-2, HIV and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induces neutralizing antibodies, Th1 CD4<sup>+</sup> T cells and CD8<sup>+</sup> T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validate that DoriVac, when conjugated with antigenic peptides or proteins, induces promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieves immune responses comparable to current mRNA vaccine platforms while potentially reducing storage constraints. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities, underscoring its potential future use.</p>

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DNA origami vaccine nanoparticles improve humoral and cellular immune responses to infectious diseases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月11日

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  • Yang C. Zeng,
  • Olivia J. Young,
  • Qiancheng Xiong,
  • Longlong Si,
  • Min Wen Ku,
  • Sylvie G. Bernier,
  • Hawa Dembele,
  • Giorgia Isinelli,
  • Tal Gilboa,
  • Zoe Swank,
  • Su Hyun Seok,
  • Anjali Rajwar,
  • Amanda Jiang,
  • Yunhao Zhai,
  • LaTonya D. Williams,
  • Caleb A. Hellman,
  • Chris M. Wintersinger,
  • Amanda R. Graveline,
  • Andyna Vernet,
  • Melinda Sanchez,
  • Sarai Bardales,
  • Georgia D. Tomaras,
  • Ju Hee Ryu,
  • Ick Chan Kwon,
  • Girija Goyal,
  • Donald E. Ingber,
  • William M. Shih

摘要

Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4+ T cell activation; however, CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurpose our DNA origami vaccine nanotechnology DoriVac to target infectious viruses, namely, SARS-CoV-2, HIV and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induces neutralizing antibodies, Th1 CD4+ T cells and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validate that DoriVac, when conjugated with antigenic peptides or proteins, induces promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieves immune responses comparable to current mRNA vaccine platforms while potentially reducing storage constraints. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities, underscoring its potential future use.