# Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

> **NIH NIH U19** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2022 · $2,223,977

## Abstract

The present application is a competing renewal of a CCHI grant on the human immune response to Bacillus
anthracis and the vaccine that protects the military, and that was first awarded in 2004. The goals of the
original application were threefold: (a) To study the human immune response to a flawed vaccine, (b) To
understand the mechanism for the high lethality of the inhalation form of the disease, (c) To understand the
cellular basis of the host response to the pathogen. We have learned much about the human vaccine with our
collection of nearly 3,000 samples, including samples of individuals who have naturally been infected with B.
anthracis. Especially notable is our finding that fully 50% of vaccinees are unprotected. This is so, despite
more than 6 vaccinations immunized against the pathogen's toxins in an onerous vaccine schedule. We have
evidence, in contrast to prevailing views, that the high rate of mortality is due to bacterial sepsis and not the
anthrax toxins. We made the seminal discovery that immune complexes of peptidoglycan and pre-existing
serum opsonins present in all humans may be the source of the massive inflammation and coagulopathy
accompanying infection by B. anthracis. We have new evidence that the infection is accompanied by release
of proinflammatory and procoagulant nucleosome material (DAMPs) and that the anthrax toxins can modulate
the clearance of this material.
In this renewal application, we will follow up on these exciting discoveries to determine:
(a) In the early- and mid-stage of disease, how are DAMPS released by the host, how they are cleared by the
host innate immune system and how does toxin affect these processes.
(b) In the late stage of the disease, how does opsonized peptidoglycan influence the outcome of the disease.
(c) Why the vaccine is imperfect in stimulating the maturation of germinal center B cells in adults.
These studies are supported by 2 scientific cores: An animal core that applies a non-human primate model we
established in previous funding cycles and a flow cytometry core with state-of-the-art sorting and analyzing
capacity. We also have a Technology Development Project that seeks to develop a generalized model by
which pathogens, including anthrax spores but also other bacterial and viral pathogens, move across epithelial
and endothelial barriers to infect tissue.
The studies in this renewal application are focused and thematically organized around the key roles of
peptidoglycan and the anthrax toxins in the human innate and adaptive immune responses. They have great
potential to identify novel means of interrupting the pathology caused by this model Gram-positive pathogen.

## Key facts

- **NIH application ID:** 10469987
- **Project number:** 5U19AI062629-19
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** A Darise Farris
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,223,977
- **Award type:** 5
- **Project period:** 2004-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469987

## Citation

> US National Institutes of Health, RePORTER application 10469987, Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax (5U19AI062629-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469987. Licensed CC0.

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