# Mechanisms of Mucosal and Systemic Immunity to Vaccination and Infection with Enteric Pathogens in Children and Adults

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $2,002,422

## Abstract

Overall - Abstract
 Enteric bacterial infections are a significant global health concern, particularly in developing nations, where
they disproportionately affect children. These diseases include typhoid fever (caused by Salmonella enterica
serovar Typhi -S. Typhi-), invasive non-typhoidal Salmonella (iNTS; e.g., S. Enteritidis, S. Typhimurium), and
shigellosis (caused by multiple Shigella serotypes). Limited knowledge of systemic and local gut immunity,
including immunological correlates of protection, for human-restricted enteric pathogens (e.g., Salmonella and
Shigella) continues to hamper vaccine development. Importantly, very limited information is available regarding
immune responses to these enteric pathogens in children. To address these major shortcomings, it is
imperative that studies involving human-restricted infectious agents are performed in children and adults. Thus,
we are proposing under the central theme of “Mechanisms of Mucosal and Systemic Immunity to Vaccination
and Infection with Enteric Pathogens in Children and Adults” to further our understanding of the protective
immunological mechanisms that can be elicited systemically and in the gut microenvironment by using
exclusively human based models with major human-restricted pathogens, i.e., Salmonella (S. Typhi, S.
Typhimurium S. Enteritidis) and Shigella flexneri 2a. These studies will use unique specimens from clinical
studies (Core 1) in which participants are immunized, or not, with parenteral or oral candidate vaccines against
these major enteric bacterial pathogens, and, in some cases, followed by challenge with wild type organisms
(Research projects -RP- 1-2). This will allow us to examine the mechanisms (e.g., epigenetic modifications)
involved in the induction and maintenance of human adaptive immunity associated with protection.
 Furthermore, because of the critical importance of innate immunity elicited in the gut, we will use explant
tissues and advanced in vitro models of the human gut mucosa (e.g., enteroids) to study the early crosstalk
between epithelial cells and innate immunity and the epigenetic mechanisms at play in the gut
microenvironment following exposure to Salmonella and Shigella (RP3). The mechanisms underlying immune
responses will be studied using advanced technologies e.g., suspension mass cytometry, imaging mass
cytometry (Core 3), EpiTOF, ATAC-seq, transcriptomics (RNA-seq), phosphoflow, and single-cell RNA-seq
(RP1-3). Mechanistic studies using unique human specimens, gut organoids and explants will employ common
methods of analysis and tools and the same wild type and attenuated bacterial strains. A world-class team of
systems biologists (Core 2) will integrate immunological and omics data. The proposed strategy involves
synergistic interactions among all RP’s and Cores supported by an interdisciplinary team of renowned
scientists in immunology, clinical studies, genomics, epigenetics, bioinformatics, modeling, biostatistics and
adjuvants. T...

## Key facts

- **NIH application ID:** 10823664
- **Project number:** 1U19AI181108-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Marcelo B. Sztein
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,002,422
- **Award type:** 1
- **Project period:** 2024-08-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823664

## Citation

> US National Institutes of Health, RePORTER application 10823664, Mechanisms of Mucosal and Systemic Immunity to Vaccination and Infection with Enteric Pathogens in Children and Adults (1U19AI181108-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10823664. Licensed CC0.

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