New vaccine platform increases rare protective B cells in preclinical study

Researchers at MIT and the Scripps Research Institute report that a DNA-based virus-like particle displaying the engineered HIV antigen eOD‑GT8 produced eightfold more on-target precursor B cells than a protein-based VLP in a humanized mouse model, and the DNA scaffold did not induce scaffold-specific antibodies.

Researchers at MIT and the Scripps Research Institute have developed a DNA-based virus-like particle that, in preclinical tests, generated larger numbers of rare precursor B cells that can evolve toward broadly neutralizing antibodies for HIV. The particle is built by DNA origami and displays multiple copies of the engineered immunogen eOD‑GT8. The team compared the DNA scaffold to a protein-based VLP used in clinical work and reported their results in Science. Anna Romanov is the paper's lead author, with Mark Bathe and Darrell Irvine as senior authors. Key findings: - In a humanized mouse model, the optimized DNA‑VLP produced eight times more "on‑target" precursor B cells than the clinical protein VLP. - The DNA scaffold did not elicit antibodies to the particle itself, unlike the protein scaffold, allowing a more focused response on the displayed antigen. - A smaller DNA‑VLP design with 60 antigen copies outperformed a 30‑copy version, with improved retention in B‑cell follicles and better helper T‑cell collaboration. - Experiments indicated the DNA particles promoted VRC01 precursor B cells toward the VRC01 antibody lineage more efficiently than the protein VLP. - The study builds on earlier DNA‑VLP work with SARS‑CoV‑2 antigens and appears in the journal Science. Summary: The reported results show that a "silent" DNA scaffold can focus antibody responses on a target HIV immunogen in a preclinical model, reducing off‑target responses seen with protein nanoparticles. The authors are investigating whether the DNA‑VLP can carry subsequent antigens for multi‑stage vaccination and whether the approach applies to other targets; further studies will be needed to determine effects beyond the reported model.