DNA Origami Breakthrough in HIV Vaccine Research

A team of researchers from Scripps Research and the Massachusetts Institute of Technology (MIT) in the United States has developed a new DNA-based scaffold for HIV vaccines that is ten times more effective than vaccines built on protein-based scaffolds, according to a study published in Science.

One of the main challenges in HIV vaccine development is encouraging the body to produce highly specific and effective antibodies. Many existing vaccine designs attach viral proteins to protein scaffolds, but these structures can provoke unintended immune reactions. Instead of focusing on the pathogen, the immune system may target the scaffold itself, reducing the vaccine’s overall effectiveness. This issue is particularly problematic when dealing with complex viruses such as HIV.

The new DNA-based approach avoids this limitation

Darrell Irvine, lead author of the study, professor at Scripps Research, and investigator at the Howard Hughes Medical Institute, described it as a completely new technology that could help scientists develop a protective HIV vaccine or address other especially difficult vaccine challenges.

Unlike protein scaffolds, DNA is considered immunologically “silent.” The immune system is naturally programmed not to react strongly to it, which helps prevent autoimmune responses. Irvine explained that while researchers already knew protein nanoparticle scaffolds could trigger their own immune responses, it was unclear how much those unwanted reactions interfered with the immune cells researchers were trying to activate.

In the study, scientists used DNA origami techniques that allow DNA to be folded into precise three-dimensional shapes. These nanoparticles displayed up to 60 copies of an HIV envelope protein designed to activate rare B cells capable of producing broadly neutralizing antibodies. Experiments were conducted on mice engineered to express human antibody genes.

Although data on DNA origami in vaccines has been limited, researchers were aware that B cells typically do not mark DNA as a target. This characteristic is partly due to the body’s need to avoid autoimmune reactions against its own genetic material.

The results were clear. Nearly 60 percent of germinal center B cells were directed specifically toward the HIV target when the DNA-based vaccine was used. In contrast, only about 20 percent showed this targeted response with protein scaffolds, where many immune cells reacted instead to the scaffold itself.

Mark Bathe, a researcher at MIT, noted that earlier work in 2024 involving a SARS-CoV-2 antigen had shown DNA scaffolds to be immunologically silent. However, it was uncertain whether they would also generate focused germinal center responses. This new study demonstrates that such a response occurs with the HIV antigen, representing a significant step forward in active immunotherapy.

Further observations strengthened the findings. Two weeks after vaccination, mice given the DNA-based vaccine showed detectable levels of the rare B cells researchers aimed to activate, while animals vaccinated with protein nanoparticles did not. Overall, the DNA approach produced a 25-fold better ratio of targeted immune cells compared with non-target cells.

The implications extend beyond HIV. Researchers noted that these vaccines are designed to recruit extremely rare B cells from the immune repertoire. As a result, DNA origami scaffolds could also play an important role in the development of universal vaccines against influenza or pancoronavirus in the future.

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(Featured image by MJH SHIKDER via Unsplash)

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First published in iSanidad. A third-party contributor translated and adapted the article from the original. In case of discrepancy, the original will prevail.

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