It not only generated a robust immune response but avoided the off-target effects sometimes seen when proteins are used.

Particulate vaccines are usually made of a scaffold of protein-based virus-like particles carrying many copies of a viral antigen. Because they mimic a natural virus, these vaccines can create a stronger immune response than traditional vaccines. They activate B cells, which produce antibodies specific to the antigen being delivered.

One potential drawback to particulate vaccines, however, is that the protein scaffolding can stimulate the production of antibodies targeting it and the antigen it's carrying, also a protein, reducing the strength of the immune system's response to the antigen. Additionally, because the body produces antibodies against the protein platform, it restricts its future use as a vaccine carrier, even for a different virus.

Now, researchers from MIT have developed a DNA-based scaffolding that avoids this issue, ensuring the immune system only responds to the antigen and not the platform.

"The DNA nanoparticle itself is immunogenically silent," said Daniel Lingwood, one of the study's corresponding authors. "If you use a protein-based platform, you get equally high-tier antibody responses to the platform and to the antigen of interest, and that can complicate repeated usage of that platform because you'll develop high affinity immune memory against it."

To create their scaffolds, the researchers adopted the 'DNA origami' technique they'd used previously, which involves folding DNA so that it mimics the structure of a virus. The technique allows the attachment of a variety of molecules, such as viral antigens, at specific locations. After attaching the receptor-binding portion of the SARS-CoV-2 spike protein to the DNA scaffold, they tested it on mice. They found the animals didn't produce antibodies to the scaffold like they did when a protein scaffold was used, only developing antibodies to SARS-CoV-2.