A major obstacle in HIV vaccine development has been the challenge of inducing the body to produce the appropriate immune cells and antibodies. Traditional vaccines often use HIV proteins attached to protein scaffolds that mimic a virus, prompting the immune system to create a variety of antibodies. However, these antibodies sometimes target the scaffold rather than HIV itself.
Researchers at Scripps Research and the Massachusetts Institute of Technology (MIT) have now introduced an innovative DNA-based vaccine scaffolding that the immune system overlooks, reducing off-target antibodies. In a study published in Science on 5 February 2026, the team demonstrated that vaccines using DNA scaffolds led to a tenfold increase in immune cells targeting a critical HIV site compared to those using protein scaffolds.
Darrell Irvine, a senior author and professor at Scripps Research, stated, “It’s a brand-new technology that might help us get to a protective HIV vaccine or solve other particularly difficult vaccine problems.” This approach utilises DNA origami technology to fold DNA into precise structures, providing a scaffold that does not trigger immune responses to itself, unlike protein scaffolds.
The study involved designing DNA nanoparticles displaying multiple copies of an HIV envelope protein, known to activate the rare B cells necessary for producing broadly neutralising antibodies against HIV. Testing in mice expressing human antibody genes showed that nearly 60% of germinal centre B cells targeted the HIV envelope protein, compared to only 20% with protein scaffolds.
This DNA-based vaccine achieved a 25-fold better ratio of HIV-specific to off-target immune cells than the protein scaffold. Within two weeks post-vaccination, mice given the DNA-based vaccine showed detectable levels of the desired rare B cells, unlike those given the protein nanoparticle-based vaccine.
The implications extend beyond HIV, as similar challenges exist in developing universal influenza and pan-coronavirus vaccines. DNA origami scaffolds could enhance the specificity of immune responses in these areas as well, according to Irvine. The ongoing research by the Irvine and Bathe teams is now exploring the impact of DNA origami shape variations on vaccine efficacy and assessing the long-term safety of these scaffolds.
