DNA origami vaccine nanoparticles improve humoral and cellular immune responses to infectious diseases
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.
Authors
- Min‐Wen Ku
- Sarai Bardales
- Donald E. Ingber (ORCID: https://orcid.org/0000-0002-4319-6520)
- William M. Shih (ORCID: https://orcid.org/0000-0002-1395-9267)
- Amanda Graveline (ORCID: https://orcid.org/0000-0002-2626-4093)
- Su Hyun Seok (ORCID: https://orcid.org/0000-0001-5951-2930)
- Zoe Swank (ORCID: https://orcid.org/0000-0001-8825-0335)
- Tal Gilboa (ORCID: https://orcid.org/0000-0001-8172-7786)
- Giorgia Isinelli (ORCID: https://orcid.org/0000-0002-1798-1576)
- Chris M. Wintersinger
- Ick Chan Kwon (ORCID: https://orcid.org/0000-0003-1272-7074)
- Anjali Rajwar
- Andyna Vernet (ORCID: https://orcid.org/0000-0003-3875-5903)
- LaTonya D. Williams (ORCID: https://orcid.org/0000-0001-8064-8533)
- Yunhao Zhai (ORCID: https://orcid.org/0000-0002-7826-217X)
- Girija Goyal
- Amanda Jiang (ORCID: https://orcid.org/0000-0001-7545-2667)
- Hawa Dembele
- C. Hellman
- Sylvie G. Bernier
- Georgia D. Tomaras
- Yang C. Zeng
- Olivia J. Young
- Qiancheng Xiong
- Melinda Sanchez
- Ju Hee Ryu
- Longlong Si
Institutions
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Duke University (US)
- Korea University (KR)
- Harvard University Press (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Center for Systems Biology (US)
- Korea Institute of Science and Technology (KR)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2026-03-11
- DOI
- https://doi.org/10.1038/s41551-026-01614-w
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- CRDF Global
- Harvard University
- National Research Foundation
- Agency for Science, Technology and Research
- Korea Institute of Science and Technology
- Korea Health Industry Development Institute
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- National Institutes of Health
- Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University