Imagine a flat square of DNA, smaller than a virus, that folds itself into shape like a piece of molecular origami. On one side it carries a molecular alarm bell that wakes up the immune system. On the other, it displays a fragment of a dangerous pathogen — say, the spike protein from SARS-CoV-2 — like a wanted poster for your immune cells to study.
That's DoriVac, a new vaccine platform developed at Harvard's Wyss Institute for Biologically Inspired Engineering. Published this month in Nature Biomedical Engineering, early results suggest it could match the immune punch of mRNA vaccines while being cheaper, more stable, and far easier to get to the places that need vaccines most.
The science behind the fold
DoriVac's building blocks are square DNA nanostructures that self-assemble from a long strand of DNA and shorter "staple" strands — the same principle behind the art of DNA origami that researchers have been refining for nearly two decades. What makes this platform special is precision: the team can control exactly where immune-stimulating molecules (called adjuvants) and target antigens sit on the structure, down to the nanometre.
"With the DoriVac platform, we have developed an extremely flexible chassis with a number of critical advantages, including an unprecedented control over vaccine composition," said William Shih, a Wyss Institute core faculty member and professor at Harvard Medical School, who led the research.
The team built DoriVac vaccines targeting conserved regions of surface proteins from SARS-CoV-2, HIV, and Ebola. In mice, the SARS-CoV-2 version triggered strong responses on both fronts that matter: antibodies to block infection, and T cells to hunt down infected cells. The HIV and Ebola versions showed similarly encouraging immune activation.
Going head-to-head with mRNA
The real headline came when researchers pitted a DoriVac vaccine carrying the full SARS-CoV-2 spike protein against the Moderna and Pfizer mRNA vaccines encoding the same protein. Using a standard booster approach in mice, both platforms produced comparable antibody and T cell responses.
But DoriVac brought something extra to the table. Unlike mRNA vaccines, which require ultra-cold storage — sometimes as low as –70°C — and complex lipid nanoparticle manufacturing, DoriVac is stable without refrigeration and simpler to produce.
The team also validated their results using a human lymph-node-on-a-chip system, a microfluidic device that mimics human immune tissue. The DoriVac vaccine activated human immune cells and triggered antigen-specific responses, suggesting the mouse results could translate to people.
Why it matters: the freezer problem
COVID-19 vaccines were a triumph of the pandemic — researchers estimate they prevented at least 14.4 million deaths in their first year. But the mRNA vaccines at their vanguard came with logistical limits. Cold chain requirements remain one of the biggest barriers to vaccine access worldwide. In England alone, roughly 4.7 million COVID vaccine doses were wasted by late 2021 due to storage and handling failures. In low- and middle-income countries, where reliable electricity and refrigeration are scarce, the challenge is far greater.
"DoriVac vaccines don't have the same cold-chain requirements as mRNA-LNP vaccines and thus could be distributed much more effectively, especially in under-resourced regions," Shih said.
A vaccine that works just as well but can travel in a backpack instead of a freezer truck could be transformative for global health equity — particularly as the WHO's Immunization Agenda 2030 pushes to close vaccination gaps worldwide.
What comes next
It's important to keep expectations grounded. DoriVac has shown promise in mice and in lab-based human tissue models, but it hasn't yet entered clinical trials in people. The leap from bench to bedside is long, and many promising platforms have stumbled along the way.
Still, the foundations are encouraging. Yang Claire Zeng, the study's first author and co-founder of DoriNano — the startup translating DoriVac toward the clinic — noted that recent studies have also shown a promising safety profile.
The mRNA revolution proved that new vaccine technology could be developed and deployed at extraordinary speed when the world needed it. DoriVac suggests the next chapter could make that protection available to everyone — no freezer required.
