# The Neuroimmunology of Viral Infection

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $440,794

## Abstract

Project Summary/Abstract
Herpes simplex virus type 1 (HSV-1) is a highly successful neurotropic virus of humans that resides in the
nervous system in a latent/persistent state. The morbidity of the virus infection resides with reactivation/re-
emergence of the virus from latency/persistence that can result in severe and life-threatening encephalitis with
profound chronic neurologic deficits in survivors. Over the past two decades, several labs have reported the
generation of vaccines to HSV-1, typically subunit vaccines consisting of one or more viral-encoded
glycoprotein. The experimental vaccines have been found to show various degrees of efficacy that primarily
focus on sterile immunity and the CD8+ T cell response. We have recently characterized a highly efficacious
vaccine, termed HSV-1 0ΔNLS, against challenge with a lethal dose of HSV-1 and found it to block virus
shedding, replication, spread, and establishment of latency in mice challenged with 10x the LD50 of HSV-1 in
comparison to naive or gD-2 subunit vaccinated mice. We propose to test the hypothesize that this
vaccine generates a highly robust and efficacious immune response primarily via the production of
neutralizing antibody that hinders virus infection, replication, and spread following primary infection,
and restores the host immune response following therapeutic application. In this application, we will fully
evaluate HSV-1 0ΔNLS against HSV-1 infection relative to local virus replication, spread to the central nervous
system (CNS), and innate and adaptive immune responses in the trigeminal ganglion (TG) and CNS following
stereotaxic injection of HSV-1 into the TG (aim 1). Furthermore, we will also characterize the role of tripartite
motif-containing 21 (TRIM21) in antibody-mediated clearance of virus from infected tissue to test the
hypothesis animals vaccinated with 0ΔNLS possess durable polyclonal antibodies (IgG) that activate the
TRIM21 pathway in cells to target virus for degradation (aim 2). The results of this study will validate the pre-
clinical application of this vaccine as an authentic candidate to further assess in the human patient.

## Key facts

- **NIH application ID:** 9830535
- **Project number:** 5R01AI053108-15
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** DANIEL J CARR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,794
- **Award type:** 5
- **Project period:** 2003-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830535

## Citation

> US National Institutes of Health, RePORTER application 9830535, The Neuroimmunology of Viral Infection (5R01AI053108-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830535. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*