DNA particles that mimic viruses hold promise as vaccines

Using a virus-like delivery particle made from DNA, researchers from MIT and the Ragon Institute of MGH, MIT, and Harvard have created a vaccine that can induce a strong antibody response against SARS-CoV-2.

The vaccine, which has been tested in mice, consists of a DNA scaffold that carries many copies of a viral antigen. This type of vaccine, known as a particulate vaccine, mimics the structure of a virus. Most previous work on particulate vaccines has relied on protein scaffolds, but the proteins used in those vaccines tend to generate an unnecessary immune response that can distract the immune system from the target.

In the mouse study, the researchers found that the DNA scaffold does not induce an immune response, allowing the immune system to focus its antibody response on the target antigen.

“DNA, we found in this work, does not elicit antibodies that may distract away from the protein of interest,” says Mark Bathe, an MIT professor of biological engineering. “What you can imagine is that your B cells and immune system are being fully trained by that target antigen, and that’s what you want — for your immune system to be laser-focused on the antigen of interest.”

This approach, which strongly stimulates B cells (the cells that produce antibodies), could make it easier to develop vaccines against viruses that have been difficult to target, including HIV and influenza, as well as SARS-CoV-2, the researchers say. Unlike T cells, which are stimulated by other types of vaccines, these B cells can persist for decades, offering long-term protection.

“We’re interested in exploring whether we can teach the immune system to deliver higher levels of immunity against pathogens that resist conventional vaccine approaches, like flu, HIV, and SARS-CoV-2,” says Daniel Lingwood, an associate professor at Harvard Medical School and a principal investigator at the Ragon Institute. “This idea of decoupling the response against the target antigen from the platform itself is a potentially powerful immunological trick that one can now bring to bear to help those immunological targeting decisions move in a direction that is more focused.”

Reference: DNA particles that mimic viruses hold promise as vaccines; Nature Communications; DOI: 10.1038/s41467-024-44869-0