# Bacteriophage virus-like particle vaccines against dengue virus non-structural protein 1

> **NIH NIH R21** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $227,250

## Abstract

PROJECT SUMMARY
Dengue virus (DENV) is a mosquito-borne flavivirus that infects over 390 million people worldwide annually,
primarily in developing nations. There are currently no antiviral treatments for DENV and prevention efforts rely
on local control of the mosquito vector, Aedes aegypti. Although efforts to develop a DENV vaccine have been
pursued for over 80 years, a safe and effective vaccine remains elusive largely due to the unique pathogenic
features of DENV infection. Recent concerns regarding the safety of Dengvaxia (Sanofi Pasteur) has
highlighted the need for novel vaccine strategies for DENV. Recent research from several groups has
implicated the viral non-structural protein 1 (NS1) in the development of vascular leakage and progression to
severe disease. NS1 is produced early in infection and is secreted in large quantities from infected cells into
the blood where it goes on to cause plasma leakage by disruption of endothelial cells in the vasculature,
mediated through direct interaction with endothelial cells and also indirect action by eliciting immune cells to
produce cytokines that cause plasma leakage. Indeed, immunization with recombinant NS1 protein or modified
NS1 proteins can protect against NS1-mediated vascular leakage. However, some antibodies produced
against NS1 have cross-reactivity to host proteins on endothelial cells and platelets, which are hypothesized to
further contribute to pathogenesis in the host. For this reason, NS1 is a promising candidate for a DENV
vaccine, but for safety reasons care should be taken to avoid eliciting potentially harmful auto-reactive
antibodies. Here, we propose to use highly immunogenic bacteriophage virus-like particle (VLP) platforms to
display short NS1 peptides as a novel vaccine strategy. This approach holds promise for eliciting high-titer,
long-lasting antibodies against NS1 that are specific for epitopes that do not elicit dangerous cross-reactive
antibodies. In Aim 1, we will engineer bacteriophage VLP-based immunogens and immunize mice to elicit
antibodies. In Aim 2, we will assess the binding characteristics of antibodies elicited by our bacteriophage
VLPs displaying NS1 peptides. In Aim 3, we will perform in vitro assessments of the antibodies elicited by the
vaccine candidates, including their ability to block NS1-mediated endothelial cell disruption and immune-cell
cytokine production. In Aim 4, we will perform an in vivo assessment of our vaccine candidates using a mouse
model of dengue virus disease. Overall these studies will establish the functions of epitope-specific antibodies
against NS1 and lead to the identification of vaccines against NS1 for eliciting protective and safe antibody
responses.

## Key facts

- **NIH application ID:** 10169244
- **Project number:** 5R21AI148836-02
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Kathryn M. Frietze
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $227,250
- **Award type:** 5
- **Project period:** 2020-05-21 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169244

## Citation

> US National Institutes of Health, RePORTER application 10169244, Bacteriophage virus-like particle vaccines against dengue virus non-structural protein 1 (5R21AI148836-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10169244. Licensed CC0.

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