# A Self-Adjuvanting Virus Like Particle Vaccine Platform for Emerging Viruses

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $747,542

## Abstract

Project Summary
The goals of this R01 proposal include the molecular and immunological characterization of vaccine adjuvant
activity associated with processes mediated by the protein Stimulator of Interferon Genes (STING). Vaccines
comprised of inert antigen are often only weakly immunogenic and thus require co-administration of adjuvants
to augment immunostimulation. Unfortunately, very few adjuvants are approved for clinical use and the
mechanisms of adjuvant-associated enhancement are poorly understood. STING is a pattern recognition
receptor that detects purine-containing cyclic dinucleotides (CDN) synthesized by either bacterial cyclases or
the host enzyme cyclic GMP-AMP (cGAMP) synthase (cGAS) following its sensing of cytosolic DNA.
Pharmacologic activation of STING greatly enhances vaccine efficacy as indicated by antibody and cell-mediated
protection against diverse microbial pathogens. Furthermore, endogenously synthesized cGAMP is naturally
released from cells in exosomes and virus particles. We exploited this phenomenon by constructing cell lines
that express constitutively active cyclases that we then used to produce immunogenic virus-like particles (VLP).
We now show that VLP derived from unrelated emerging flavi- and alphaviruses efficiently encapsulate bioactive
CDN and stimulate STING-dependent activity in vivo. Since extracellular CDNs are highly susceptible to
degradation and disperse quickly from the site of injection, we hypothesize that this simple approach represents
a transformative technological improvement for harnessing STING-directed adjuvant effects in the draining
lymph node. We also predict this will be a highly adaptable platform and propose to explore the extent to which
it is applicable to potentially emerging virus types. Experimentally, this also represents a unique investigative
model that will allow in vivo characterization of the innate and molecular correlates of adaptive immunity that are
potentiated by targeted STING activity. We thus hypothesize that the enhancement of antigen-directed immune
responses by STING-based adjuvants is functionally linked to key molecular and cellular processes that are
discernable using our proposed vaccines and experimental systems. We plan to explore this using an integrated
approach that uses molecular transcriptomic analysis, mouse models of immune profiling, and nonhuman
primate models of viral growth and protective immunity devised by our group.

## Key facts

- **NIH application ID:** 10862875
- **Project number:** 5R01AI177293-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** VICTOR Robert DEFILIPPIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,542
- **Award type:** 5
- **Project period:** 2023-06-08 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862875

## Citation

> US National Institutes of Health, RePORTER application 10862875, A Self-Adjuvanting Virus Like Particle Vaccine Platform for Emerging Viruses (5R01AI177293-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10862875. Licensed CC0.

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