# Immune Tolerance Network

> **NIH NIH UM1** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2021 · $1,255,142

## Abstract

Project Summary/ Abstract
BCG can induce epigenetic changes in the innate immune system with non-specific memory characteristics,
termed `trained immunity', associated with enhanced immune responses to heterologous infections and
vaccines. We hypothesize that the enhanced immunity induced by BCG vaccination will provide protection for
high-risk individuals against COVID-19 and other viral respiratory infections. This hypothesis will be assessed
by conducting a Phase II double blind, randomized, placebo (vehicle)-controlled clinical trial of BCG Tokyo
172-1 (BCG-Japan) vaccine for the prevention of COVID-19 in healthcare workers (HCWs at high-risk for
infection. BCG-Japan is one of the most potent formulations of BCG vaccine demonstrating relatively high
microbial viability and human innate immune activation, and offering robust protection against TB and multiple
off-target infections. This study will test the hypothesis that administration of BCG-Japan vaccine to HCWs at
high-risk for infection will enhance innate antiviral immunity to reduce the risk for SARS-CoV-2 .infection and/or
severity of COVID-19. Two thousand and eight hundred (2,800) eligible volunteer HCWs will be randomly
assigned to either a placebo vaccination or BCG-Japan, conducted at Brigham & Women's Hospital and up to
four additional clinical sites. Subjects will be monitored for two years with assessments for viral illness and
serological and molecular monitoring for SARS-CoV-2. A subset of subjects will be intensively studied using a
suite of systems biology analyses, which will be integrated with clinical data to gain insight into the impact of
BCG on human immunity in relation to SARS-CoV-2 infection and/or incidence or severity of COVID. Overall
this aspect will provide information regarding how BCG may reshape the human blood and nasal mucosal
compartments in a manner that may correlate with protection against SARS-CoV-2 infection and/or incidence
and severity of COVID.

## Key facts

- **NIH application ID:** 10331451
- **Project number:** 3UM1AI109565-07S2
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** GERALD T NEPOM
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,255,142
- **Award type:** 3
- **Project period:** 2014-02-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331451

## Citation

> US National Institutes of Health, RePORTER application 10331451, Immune Tolerance Network (3UM1AI109565-07S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10331451. Licensed CC0.

---

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