DNA origami vaccine (DoriVac) nanoparticles improve both humoral and cellular immune responses to infectious diseases.

Yang C Zeng, Olivia J Young, Qiancheng Xiong, Longlong Si, Min Wen Ku, Sylvie G Bernier, Hawa Dembele, Giorgia Isinelli, Tal Gilboa, Zoe Newell 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

bioRxiv : the preprint server for biology 2025 Apr 04

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Current SARS-CoV-2 vaccines have demonstrated 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 repurposed our DNA origami vaccine nanotechnology, DoriVac, for targeting infectious viruses, namely SARS-CoV-2, HIV, and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 (HR2) peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induced neutralizing antibodies, Th1 CD4+ T cells, and CD8+ T cells in naïve mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validated that DoriVac, when conjugated with antigenic peptides or proteins, induced promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieved 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 utility in addressing future pandemics.

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PMID: 38260393

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