# Investigation of Synthetic DNA-based Viral Particles for Spatially Controlled Antigen Presentation

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $387,750

## Abstract

PROJECT SUMMARY
Strategies to enhance antigenicity, antibody affinity maturation, and memory induction in response to subunit
vaccines are of broad relevance for the design of effective vaccines against infectious diseases, and may be
especially important for difficult-to-neutralize pathogens such as HIV. One approach to enhance the efficacy of
subunit vaccines is to formulate antigens in a multivalent, nanoparticulate form, which promotes several aspects
of humoral immunity, and most notably enhances crosslinking of B cell receptors (BCRs). This approach has
been exploited both in licensed vaccines (e.g., the HPV and HBV vaccines), and in a great variety of vaccines
in preclinical and clinical development. However, to date it remains unclear what are the ideal characteristics of
nanoparticle antigen display. In this project, we use the unique technology of scaffolded DNA origami to engineer
nanoparticles on the 10–100 nanometer scale that offer the ability to investigate the impact of scaffold size,
antigen copy number up to more than 100, antigen-BCR affinity, as well as the nanoscale spatial organization
and dimensionality of antigen presentation on BCR activation. Specifically, we test the relative importance of
these parameters on B-cell activation, which are of central importance to the development of a successful subunit
vaccines, using the germline targeting engineered outer domain of HIV-1 gp120, termed eOD-GT8, and its
variants with different affinities, as a testbed. In vitro evaluation of early B-cell signaling and pathway activation
will be characterized, and contrasted with the benchmark strongly activating 60-mer control organized on a
protein scaffold. Single-cell fluorescence imaging is used to investigate the detailed mechanism of BCR-binding
and B-cell activation based on the optimal immunogen presentation found. These constructs are then used to
test the impact of these optimal HIV DNA-NP constructs on T-cell and B-cell response in vivo using mouse
models. Taken together, our results will offer the elucidation of the optimal immunogen presentation parameters
for effective immune cell response in the development of more effective subunit vaccines, with major translational
potential for HIV and other infectious diseases.

## Key facts

- **NIH application ID:** 10460559
- **Project number:** 5R01AI162307-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mark Bathe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,750
- **Award type:** 5
- **Project period:** 2021-08-02 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460559

## Citation

> US National Institutes of Health, RePORTER application 10460559, Investigation of Synthetic DNA-based Viral Particles for Spatially Controlled Antigen Presentation (5R01AI162307-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10460559. Licensed CC0.

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