Image credit: Bannard and Howarth. (2026)
Despite the current public image challenges surrounding vaccines, progress in basic science and application continues to advance rapidly. A particularly significant development was published in the February 6, 2026 issue of Science (Romanov et al., 2026). This research work combines a novel molecular technology known as DNA origami with precise antigen manipulation to develop a potent and broadly protective HIV vaccine. In this blog I will describe, in brief, the techniques and why it is so exciting.
The Paradoxical and Complicated Road to Broadly Neutralizing Antibodies
Despite decades of research, a fully protective vaccine against human immunodeficiency virus (HIV) remains elusive due to the unstable nature of the major surface antigen of the virus, its envelope glycoprotein (Env) (Bannard and Howarth, 2026). While HIV infection elicits a strong antibody response, these molecules are typically not broadly neutralizing (bnAbs). Although bnAbs can develop naturally in some patients, they generally develop too late to prevent chronic infection. However, when administered, exogenous bnAbs have proven to be a very effective defense against infection.
Current research indicates that the path to generating bnAbs requires, paradoxically, targeting rare, immunologically subdominant B cell clones that respond to particular antigens with a relatively lower affinity (Bannard and Howarth, 2026). These B cells then form germinal centers (GCs) and undergo affinity maturation through numerous rounds of somatic hypermutation (SHM) within germinal centers. To facilitate this process, a synthetic antigen, derived from a domain of Env and called eOD-GT8, has been engineered. This eOD-GT8 protein antigen has been designed to bind specifically to the VRC01-subclass of B cell receptors with high affinity while minimizing the production of non-neutralizing antibodies. VRC01 has been considered a cornerstone in the development of effective HIV vaccines and therapies.
Figure 1: Schematic of DNA origami-engineered nanomaterials and applications (Image credit: Zhan et al., (2023)
DNA origami is self assembling structure programmed by its sequence
Pioneered in the early 1980s, DNA origami involves engineering large molecules and nanomaterials using DNA building blocks (Zhan et al., 2023, for a schematic see Figure 1). This field is driven by the ease of DNA fabrication, the predictable structure of DNA double helices, and the molecule’s relative stability. Recent advancements in DNA origami have expanded achievable structures from simple shapes to complex designs for use in medicine, electronics, sensing, and nanomachinery (Zhan et al., 2023). It is now possible to create 3D icosahedral, virus-like nanoparticles (DNA-VLP) from specific DNA strands. These can be engineered with sites for click chemistry crosslinks to incorporate protein epitopes.
Virus-Like Particles Are Effective Immunogens
Significant advances in HIV vaccine antigen design have been achieved through the creation of molecules such as eOD-GT8. These antigens become far more powerful immunogens when presented in high density on larger molecular scaffolds. Previous state-of-the-art versions of these virus-like particles (VLP) utilize self-assembling scaffold proteins to link multiple copies of the original antigen, driving a more efficient response through multiple antigen crossovers with B-cell receptors. Furthermore, these multimeric antigens enhance uptake, T cell presentation, and GC activities, all of which increase immunogenicity (Bannard and Howarth, 2026). However, a notable downside is that these protein-based VLP scaffolds can themselves become targets for the host immune system. This leads to several negative consequences:
- Induced anti-scaffold antibodies can make subsequent immunizations using the same scaffold less effective.
- The anti-scaffold immune response runs the risk of depleting limited T helper cell populations needed to drive a maximal response to the primary HIV antigen.
DNA Origami versus protein VLP
Recent work by Romanov et al., (2026) highlights the development of the “d40-30mer,” a DNA origami molecule designed to display 30 copies of the eOD-GT8 antigen. While this structure elicits antibody titers ten times higher than the eOD-GT8 monomer with minimal anti-DNA antibody response, it initially trailed behind the clinical protein nanoparticle (p60mer) in priming germinal center (GC) activity.
Romanov and team (2026) initially compared the d40-30mer to the clinical protein nanoparticle p60mer, noting that the d40-30mer was less efficient in fully priming GC activity. To address this, the group developed three additional DNA-VLP with alternative epitope densities (see Figure 2). The d30-60mer version proved superior and was further optimized by incorporating a synthetic T cell epitope (d30-60mer-PADRE). This optimized version generated three times as many GC B cells than p60mer and demonstrated a significantly higher ratio of epitope-specific versus scaffold-specific GC B cells. Most importantly, it was more effective at priming and expanding rare bnAb precursor GC B cells.
Figure 2: Depicted are four types of engineered nanoparticles designed for HIV vaccine research, specifically focusing on the display of the eOD-GT8 (engineered Outer Domain-Germline Targeting) immunogen (Image credit: Romanov et al., (2026))
While further research is needed to determine the clinical superiority and optimal administration of these DNA-VLPs, these results are a strong indicator for future promise.
Companies Currently Developing or Offering DNA Origami Products
DoriNano: Founded in 2022 as a Harvard Wyss Institute spin-out, this Boston-based company develops immunotherapies using a square-block DNA origami platform for the simultaneous delivery of antigens and CpG oligonucleotides. Their current pipeline includes:
- DoriVac-101: for Head and Neck Squamous Cell Carcinoma.
- DoriVac-102: for High-Grade Serous Ovarian Cancer.
GATTAquant: Headquartered in Munich, Germany and founded in 2014 from the Technical University of Braunschweig, GATTAquant specializes in DNA origami-based nanorulers for super-resolution microscopy:
- GATTA-SIM NANORULER: 120 to 160nm range developed for Structured Illumination Microscopy (SIM).
- GATTA-STED NANORULER: 50 to 120nm range developed for Stimulated Emission Depletion (STED) microscopy.
- GATTA-CONFOCAL NANORULER: 350nm size and available with multiple colored fluorophores developed for standard confocal microscopy.
Plectonic Biotech: A Munich-based company founded in 2023, Plectonic utilizes DNA origami to create a synthetic antibody carrier platform. Their current focus is on “LOGIBODY” (LOGIc-gated AntiBODY) technology, with research programs targeting hematologic cancers and solid tumors.
References
Bannard and Howarth, A double helix twist in HIV vaccine design. (2026) Science, Feb 5;391(6785):553-554.
Romanov et al., DNA origami vaccines program antigen-focused germinal centers. (2026) Science, Feb 5;391(6785):eadx6291. doi: 10.1126/science.adx6291. Epub 2026 Feb 5.
Zhan et al., Recent Advances in DNA Origami-Engineered Nanomaterials and Applications. (2023) Chem Rev, Apr 12;123(7):3976-4050.
