# Development of B Cell Responses and Markers of Immunity Following Oral Rotavirus Vaccination in Infants

> **NIH NIH P20** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $266,250

## Abstract

PROJECT SUMMARY
Rotavirus (RV) remains the leading cause of death due to diarrheal disease in children worldwide, with a
disproportionate burden of severe and fatal disease in low-income countries of sub-Saharan Africa and Asia.
Oral RV vaccines such as Rotarix (GlaxoSmithKline) are highly efficacious in high-income countries, but for
unclear reasons they significantly underperform in low-income countries, a significant obstacle to the reduction
of diarrheal disease worldwide. Greater understanding of why oral vaccines fail in these settings is needed to
improve vaccine performance and develop next-generation vaccines. The goal of this study is to refine
approaches for assessing immunological responses to oral vaccines, using rotavirus (RV) as a prototype.
Generation of pathogen-specific immunological memory is the fundamental goal of vaccination, but little is
known about the ability of RV vaccines to do this. Since antibody responses have consistently been shown to
be critical for RV immunity, assessment of B cell responses to RV vaccination is paramount, particularly the
generation of RV-specific memory B cells. However, evaluations of RV-specific lymphocyte responses to
currently licensed vaccines are completely lacking. The hypothesis is that under proper conditions (e.g. in high-
income countries), circulating RV-specific B cell subsets reflecting immune memory can be identified following
vaccination. Similarly, the project proposes that oral RV vaccine underperformance in low-income settings is
due to a failure of the vaccine to generate memory B cell responses, and that this may be mediated in part by
early B cell exhaustion due to the increased gut pathogen burden unique to these settings.
To test these hypotheses, flow cytometry will be used to define the immunophenotype of circulating RV-
specific B among infants in Burlington, VT, USA and Dhaka, Bangladesh following oral RV vaccination. These
cohorts represent populations in which vaccine responses are excellent (VT) and diminished (Bangladesh).
RV-specific subsets thus identified will be correlated with serum antibody responses and fecal vaccine
shedding, surrogate markers of vaccine effect. Next, the project will evaluate the contribution of cofactors
thought to impact RV vaccine performance on the development of RV-specific B cells. Finally, computational
models of RV-specific vaccine responses will be developed, and the experimental results will be applied to
iteratively test and refine these models to generate a predictive model of RV immunity.
These results will lead to greater understanding of the development of immunity to RV and other enteric viral
infections and identify key targets for intervention to improve oral vaccine performance around the world.

## Key facts

- **NIH application ID:** 10476546
- **Project number:** 5P20GM125498-05
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Benjamin Lee
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $266,250
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476546

## Citation

> US National Institutes of Health, RePORTER application 10476546, Development of B Cell Responses and Markers of Immunity Following Oral Rotavirus Vaccination in Infants (5P20GM125498-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10476546. Licensed CC0.

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