New Vaccine Platform Promotes Rare Protective B Cells

MIT and Scripps researchers develop a DNA-based vaccine that generates more of the desired B cells for HIV antibodies than a protein-based vaccine.

Published on Feb. 6, 2026

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Researchers at MIT and the Scripps Research Institute have developed a vaccine that uses DNA instead of protein as a scaffold to fabricate a virus-like particle (VLP) displaying an engineered HIV immunogen. This DNA-based VLP generated substantially more precursor B cells capable of evolving to produce broadly neutralizing antibodies compared to a protein-based VLP that has shown success in human clinical trials.

Why it matters

Generating antibodies that can neutralize multiple strains of HIV is a longstanding goal of vaccine research. This new DNA-based vaccine platform could be a breakthrough in focusing the immune response on the desired target B cells, which are exceptionally rare, and may transform vaccine design for challenging diseases like HIV.

The details

The researchers' vaccine design uses DNA instead of protein as a scaffold to fabricate a virus-like particle (VLP) displaying numerous copies of an engineered HIV immunogen called eOD-GT8. Preclinical studies showed this DNA-VLP generated eight times more of the desired, or "on-target," B cells than a protein-based VLP that has shown significant success in human clinical trials. The researchers also found the DNA scaffold does not induce an immune response when applied to the engineered HIV antigen, meaning the DNA VLP might be used to deliver multiple antigens when boosting strategies are needed.

  • The study appears today in Science.

The players

Mark Bathe

An MIT professor of biological engineering and an associate member of the Broad Institute of MIT and Harvard.

Darrell Irvine

A professor of immunology and microbiology at the Scripps Research Institute and a Howard Hughes Medical Institute Investigator.

Anna Romanov

The study's lead author, who is a PhD student.

William Schief

A professor of immunology and microbiology at Scripps and the vice president for protein design at Moderna.

Gabriel Victora

A professor of immunology, virology, and microbiology at Rockefeller University.

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What they’re saying

“We were all surprised that this already outstanding VLP from Scripps was significantly outperformed by the DNA-based VLP. These early preclinical results suggest a potential breakthrough as an entirely new, first-in-class VLP that could transform the way we think about active immunotherapies, and vaccine design, across a variety of indications.”

— Mark Bathe, MIT professor of biological engineering (Science)

“The DNA-VLP allowed us for the first time to assess whether B cells targeting the VLP itself limit the development of 'on target' B cell responses - a longstanding question in vaccine immunology.”

— Darrell Irvine, Professor of immunology and microbiology at the Scripps Research Institute (Science)

“In the field of vaccine immunology, the question of whether B cell responses to a targeted protective epitope on a vaccine antigen might be hindered by responses to neighboring off-target epitopes on the same antigen has been under intense investigation. This study shows quite convincingly that reducing off-target responses by using a DNA VLP can improve desired on-target responses.”

— William Schief, Professor of immunology and microbiology at Scripps (Science)

“DNA-based particles that leverage B cells' natural tolerance to nucleic acids are a clever idea to circumvent this problem, and the research team's elegant experiments clearly show that this strategy can be used to make difficult epitopes easier to target.”

— Gabriel Victora, Professor of immunology, virology, and microbiology at Rockefeller University (Science)

What’s next

The researchers are currently investigating using the DNA-VLP to carry second and potentially third antigens needed in the vaccine series.

The takeaway

This new DNA-based vaccine platform could be a breakthrough in focusing the immune response on rare but desired target B cells, transforming vaccine design for challenging diseases like HIV and potentially other applications such as flu, chemical warfare agents, or neurodegenerative diseases.