# Improving survival from Burkholderia pseudomallei and other pathogenic intracellular bacteria

> **NIH NIH R43** · BOLDER BIOTECHNOLOGY, INC. · 2024 · $295,924

## Abstract

Abstract. Burkholderia pseudomallei (Bpm) is a facultative intracellular bacterium that is the causative agent
of melioidosis. Bpm is a CDC Tier 1 Select agent, which a biological agent that has been determined to have
the potential to pose a severe threat to public health and safety. NIAID classifies Bpm as a Category B
pathogen, which is a pathogen that provides the highest risk to national security and public health due to its
ease of dissemination, high mortality rate, and potential use as a bioterrorism weapon. There are no approved
treatments or vaccines to protect against acute or chronic Bpm infection, and the genus is resistant to most
antibiotics. Thus, there is an urgent need for new medicines to treat Bpm infection. Vaccines in general 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. A
concern for both vaccines and antibiotics is that resistant Bpm strains may develop through random or directed
mutation such as for a bioweapon. An alternative and potentially synergistic approach for protecting against
Bpm infection is to stimulate the innate arm of the host immune system to resist infection. Interferon gamma
(IFN-) is a critical component of the innate immune system and has been shown to be absolutely required for
protection from Bpm lethality. IFN- quickly (within hours) activates host cells to resist infection by Bpm and
other deadly facultative intracellular bacteria such as Tularemia, protozoa like toxoplasma, and viruses like
Ebola. Thus, IFN- has the potential to be an effective broad-spectrum treatment against several deadly
bioterrorism threats. However, IFN- has a very short in vivo half-life, poor bioavailability, and requires
intraperitoneal (ip) injection to reach protective plasma levels in mice, which limit the protein's utility as a Bpm
therapeutic. Subcutaneous (sc) dosing of IFN- results in ~ 10-fold lower plasma levels and greatly reduced in
efficacy. We created site-specific PEGylated human and mouse IFN- analogs (PEG IFN-) that have superior
bioavailability and > 20-fold longer half-lives than IFN- following sc dosing. The PEG murine IFN- homolog
proved significantly more efficacious than mIFN- at improving survival from Ebola virus infection following sc
injection in mice. We hypothesize PEG-IFN- also will be significantly more effective than IFN- at preventing
morbidity and mortality from Bpm infection when administered by sc injection and will test this hypothesis by
evaluating efficacy of PEG mIFN- and mIFN- using a well characterized murine Bpm infection model. These
studies will lead to a fast-acting treatment that confers protection within hours and which can be administered
easily by sc injection to patients who recently contracted Bpm, as well as potentially to first responders and
healthcare providers in an emergency ...

## Key facts

- **NIH application ID:** 10822404
- **Project number:** 1R43AI181293-01
- **Recipient organization:** BOLDER BIOTECHNOLOGY, INC.
- **Principal Investigator:** George Norbert Cox
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $295,924
- **Award type:** 1
- **Project period:** 2024-02-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10822404

## Citation

> US National Institutes of Health, RePORTER application 10822404, Improving survival from Burkholderia pseudomallei and other pathogenic intracellular bacteria (1R43AI181293-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10822404. Licensed CC0.

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