# Naso-oropharyngeal Brucella Infections and Mucosal Immune Protection

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $376,886

## Abstract

ABSTRACT
Human brucellosis ranks third among 8 neglected zoonotic diseases, and is contracted as a result of ingesting
unpasteurized dairy products. The Gram-negative Brucella is highly infectious, and is believed that less than 2000
CFUs are needed for pulmonary infection. Infection primarily occurs following a mucosal exposure causing a
systemic disease manifested by its flu-like symptoms. Despite aggressive antibiotic treatment, it can still persist
in a recurring sequelae evident as undulant fever and arthritis. Brucellae survival within the host is linked to its
ability to evade intracellular recognition, thus, allowing them to sequester in various tissues. Although human
disease is mostly acquired via a mucosal exposure, few studies have examined mucosal immunization for
brucellosis. In part, this is attributed to the inefficiency of oral gavage methods requiring an enormous amount
of brucellae to induce an infection. Bearing this, we have devised an oral infection method, termed ad bibitum,
that retains the infection to the oral mucosa and draining head and neck lymph nodes (HNLNs) recapitulating
natural human infections. Hence, we hypothesize that mucosal immunization of the naso-oropharyngeal tissues
will derive the required correlates of protective immunity using our novel attenuated Brucella melitensis (BM) strain.
Such approaches will allow for the comparison of which immune cell types are needed for protection and to
reverse wild-type (wt) BM infection from mounting regulatory responses in order to evade detection. Subsequent
to immunization, the attenuated BM mutant stimulates increases in IFN-g- and TNF-a-producing CD4+ and CD8+
T cells, which can effectively eliminate the brucellae. To further these studies, three Specific Aims are proposed.
 Studies in Specific Aim 1 will establish a mucosal naso-oropharyngeal vaccination regimen that confers protection
against mucosal challenge with virulent Brucella. Studies in Specific Aim 2 will determine which T cell subsets are
responsible for protection in the mucosal and systemic compartments. Studies in Specific Aim 3 will establish the
role for mucosal memory CD8+ T cells in augmenting protection against virulent Brucella challenge more effectively
than CD4+ T cells. These studies will further our understanding of how to induce immunity in the naso-
oropharyngeal mucosa, and will aid in devising strategies to circumvent BM' evasion methods. This work will
ultimately define what constitutes protection and which T cells are needed to guard against wt BM challenges.

## Key facts

- **NIH application ID:** 9977090
- **Project number:** 5R01AI125516-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** David W Pascual
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,886
- **Award type:** 5
- **Project period:** 2017-08-17 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977090

## Citation

> US National Institutes of Health, RePORTER application 9977090, Naso-oropharyngeal Brucella Infections and Mucosal Immune Protection (5R01AI125516-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977090. Licensed CC0.

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