# Immune Mechanisms Regulating the Development of Systemic and Mucosal Antigen-specific B Cells After Vaccination and Challenge in Humans

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $427,045

## Abstract

CCHI Research Project 2 – Abstract
Shigellosis and salmonellosis continue to be serious public health problems affecting primarily young children in
developing countries; however, adults are also susceptible to these pathogens. The emergence of multi-drug
and extensively drug-resistant Shigella and Salmonella strains has created a sense of urgency for the
development of effective vaccines. However, the lack of information on the development of mucosal immunity
has hindered novel vaccine design. To date, it is unclear to what extend the immunity measured in peripheral
blood is representative of the gut mucosal immunity. Recent studies have shown that immunity in local tissues
is critical for protection from disease. The recently described resident memory B cells are likely the first line of
defense against re-infection at the tissue level. The overall goal of Research Project (RP2) is to characterize and
compare the mechanisms that drive the development of systemic and mucosal B cell immunity to human-
restricted enteric pathogens using state-of-the-art immunological and genomics methods. To this end, unique
human specimens (Core 1) will be used including a) PBMC from volunteers immunized parenterally with
conjugate vaccines against Salmonella (TSCV) and Shigella (SF2s-TT15); b) PBMC from volunteers immunized
with oral vaccines against Salmonella (Ty21a) and Shigella (CVD 1208S-122); c) PBMC from S. flexneri 2a
challenge studies; d) PBMC and terminal ileum biopsies from adult Ty21a vaccinees; and e) PBMC from children
immunized with Ty21a. Our overall hypothesis is that antigen-specific mucosal B cell responses differ in
magnitude and characteristics to those in peripheral blood and that oral immunization favors responses
associated with protection and these responses are also age dependent. In Aim 1, we will characterize Shigella-
and Salmonella-specific B cells in PBMC after parenteral and oral immunizations. Aim 2 will characterize B cell
immunity (PBMC) after a wt Shigella challenge. Aim 3 will characterize Salmonella-specific B cell responses
after oral vaccination at the systemic (PBMC) and local (gut mucosa) levels. Aim 4 will explore Salmonella-
specific B cell responses (PBMC) in children (<18 yo). In all aims, the mechanisms involved will be studied by
evaluating changes in phenotype, gene expression (transcriptome), epigenome (EpiTOF), and/or BCR-
sequence profiles (LIBRA-seq) in bacteria-specific B cells after vaccination/challenge. Additionally, Aim 3 will
incorporate imaging mass cytometry (Core 3) to study Salmonella-specific B cells and their interaction(s) with
other immune cells at the tissue level. Bacteria-specific B cells will be identified using a unique set of reagents
developed to study enteric pathogens (e.g., bacteria with fluorescent tags). The rich data sets will be analyzed,
compared and integrated in collaboration with the Systems Biology and Biostatistics Core (Core 2). Data
integration will include results from RP1-...

## Key facts

- **NIH application ID:** 10823671
- **Project number:** 1U19AI181108-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Franklin R. Toapanta
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,045
- **Award type:** 1
- **Project period:** 2024-08-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823671

## Citation

> US National Institutes of Health, RePORTER application 10823671, Immune Mechanisms Regulating the Development of Systemic and Mucosal Antigen-specific B Cells After Vaccination and Challenge in Humans (1U19AI181108-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10823671. Licensed CC0.

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