# Interferon-beta as an Adjuvant for Tolerogenic Vaccination

> **NIH NIH R01** · EAST CAROLINA UNIVERSITY · 2020 · $416,673

## Abstract

Project Summary
This proposal will focus on the development of tolerogenic vaccines that elicit responses of FOXP3+ regulatory T cells
(Tregs) in murine models of EAE. This program will develop novel tolerogenic vaccines based on the use of Interferon-
beta (IFN-β) as a tolerogenic adjuvant. Preliminary data indicated that these tolerogenic vaccines elicited a major
FOXP3+ regulatory T cell (Treg) population because a single tolerogenic vaccination directly elicited FOXP3+ Tregs in
vivo. Treatment of mice with an anti-CD25 mAb that depleted Tregs reversed vaccine-induced tolerance. Also, IFN-β-
induced Tregs mediated the adoptive transfer of resistance to EAE. Three repeated immunizations with the tolerogenic
vaccine elicited a persistent memory/ effector Treg subset. Our hypothesis is that tolerogenic vaccination drives tolerance
via the induction of FOXP3+ Tregs and culminates in the induction of CTLA-4+ effector Tregs and a mechanism of infec-
tious tolerance. Aim 1 will test whether tolerogenic vaccination elicits polyclonal tolerance to NAg peptides by a mecha-
nism dependent upon NAg-specific FOXP3+ Tregs. The approach will test multiple myelin peptides for tolerogenic vac-
cination of transgenic TCR model systems in combination with FOXP3-reporter, fate-mapping Treg models and Treg de-
pletion strategies to assess tolerance induction, function, phenotype, and stability of vaccine-induced Treg populations.
Aim 2 will assess induction and effector mechanisms of IFN-β induced FOXP3+ Tregs. Aim 2a will test whether IFN-β
based tolerogenic vaccines elicit `naïve', `central' or `effector' FOXP3+ T cells when the Type I IFNAR is absent in mye-
loid cells, dendritic cells, pan T cells, or FOXP3+ T cells. Aim 2b will test whether IFN-β and NAg elicit FOXP3+ T cells
that express the hallmarks infectious tolerance. The aim is based on the observation that CD45.2 FOXP3+ 2D2-FIG Tregs
effectively directed the nascent differentiation of a naïve population of FOXP3(null) CD45.1 T cells into a major FOXP3+
population in mixed activation cultures. The proposed research will provide novel information on tolerogenic vaccination
and infectious tolerance via suppressive epitope spread among the major, MS-associated myelin NAg epitopes.

## Key facts

- **NIH application ID:** 9904465
- **Project number:** 5R01AI126398-05
- **Recipient organization:** EAST CAROLINA UNIVERSITY
- **Principal Investigator:** Mark D. Mannie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,673
- **Award type:** 5
- **Project period:** 2016-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904465

## Citation

> US National Institutes of Health, RePORTER application 9904465, Interferon-beta as an Adjuvant for Tolerogenic Vaccination (5R01AI126398-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9904465. Licensed CC0.

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