DNA origami vaccine nanoparticles improve 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 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, …William M. Shih

https://www.nature.com/articles/s41551-026-01614-w?utm_medium=email&_hsenc=p2ANqtz--IfJSyYHc0U7-oUr667PyekarXQaUk6sxxhiyhUjE5ZRS2-6ts9GfkD-655BWV1_ebhztY_1xUnTAyS9NaMkjFcubrDQ&_hsmi=136907737&utm_content=136917285&utm_source=hs_email 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.