# Stimulating innate immunity to protect against Ebola virus infection

> **NIH NIH R43** · BOLDER BIOTECHNOLOGY, INC. · 2021 · $300,000

## Abstract

Abstract. Filoviruses such as Ebola and Marburg viruses are Category A pathogens (pathogens that provide
the highest risk to national security and public health) on NIAID's list of emerging infectious diseases due to
their ease of dissemination, high mortality rates, and potential use as bioterrorism weapons. There is a need
for fast acting, easy to use, and more effective medicines to protect against and improve survival from Ebola
virus infection. Vaccines in development require at least 10 days for subjects to develop immunity and thus are
not useful for treating newly infected patients or protecting non-vaccinated healthcare providers and first
responders in an emergency outbreak situation. Antibiotics and antibody cocktails under study require
intravenous infusion and resistance may develop through random or directed virus mutation. An alternative and
potentially synergistic approach for protecting against Ebola virus infection is to stimulate the innate arm of the
host immune system to resist viral infection. Macrophages and dendritic cells typically are the first cells
infected by Ebola virus. Upon entry, the virus replicates and expresses proteins that interfere with the host
cell's ability to block viral infection. The virus also causes host cells to secrete proinflammatory cytokines and
chemokines that attract other myeloid cells to propagate the infection and results in a dysfunctional immune
response unable to control the virus. Interferon gamma (IFNG) quickly (within hours) activates macrophages
and dendritic cells so that they resist infection by Ebola and other viruses, as well as infection by several
Category A facultative intracellular bacterial pathogens such as Tularemia and Burkholderia. Thus, IFNG has
the potential to be an effective therapy against several deadly bioterrorism threats. However, IFNG has a very
short in vivo half-life, poor bioavailability, required intraperitoneal injection for efficacy in preclinical studies, and
has a narrow efficacy window, all of which limit the protein's utility as an Ebola therapy. We created a long-
acting human IFNG analog (PEG IFNG) that has superior bioavailability and a longer half-life following
subcutaneous injection and significantly greater efficacy than IFNG in animals. We hypothesize PEG-IFNG will
be significantly more effective than IFNG at preventing morbidity and mortality from Ebola virus infection both
as a protectant for pre-exposure prophylaxis and as a mitigator for post-exposure prophylaxis. We will test this
hypothesis by comparing efficacy of a murine PEG IFNG homolog and murine IFNG administered pre and post
infection for reducing morbidity and mortality from lethal Ebola virus infection in mice, as measured by survival,
weight gain and clinical sickness scores. These studies will lead to an effective treatment that confers
protection within hours and which can be administered easily (subcutaneous injection) to patients who recently
contracted Ebola virus, as well...

## Key facts

- **NIH application ID:** 10325941
- **Project number:** 1R43AI157684-01A1
- **Recipient organization:** BOLDER BIOTECHNOLOGY, INC.
- **Principal Investigator:** George Norbert Cox
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2021-07-02 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10325941

## Citation

> US National Institutes of Health, RePORTER application 10325941, Stimulating innate immunity to protect against Ebola virus infection (1R43AI157684-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10325941. Licensed CC0.

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