# Gut microbial and metabolic mediators of rotavirus vaccine response

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $551,221

## Abstract

Abstract
Rotavirus (RV) infection causes life-threatening, dehydrating diarrhea and is the leading cause of diarrheal
deaths among children <5 years old despite availability of a vaccine. Critically, the oral vaccine is less effective
in middle- and low-income countries where disproportionately more deaths occur compared to high-income
countries. Addressing this disparity in vaccine effectiveness is a major public health priority. Correlates of
protection do not exist, and cellular responses against RV in humans remain incompletely understood.
Mounting evidence supports a direct role for the gut microbiota in modulating humoral and cellular immune
responses to oral vaccines, but little is known about their actual mechanism of action. In our pilot study,
vaccine responders had a significantly greater abundance of Bifidobacterium longum and higher content of
microbial genes associated with folate transformation in their gut compared to nonresponders. These data
suggest that infants may depend on microbes such as B. longum to synthesize folate de novo as a mechanism
for RV-specific immune cell expansion. We hypothesize that de novo folate synthesis by microbes such
as B. longum facilitates RV-specific immune cell expansion, and that levels of folate modulate vaccine
immunogenicity. We propose to study 330 infants from the US, Panama, and Peru where vaccine efficacy is
known to be high, medium and low, respectively, by using both stored and prospectively collected longitudinal
samples of blood and stool from infants 0 to 12 months of age. We have designed a novel RV “megapool” of
immunogenic peptides to define cellular immune responses to RV vaccination in addition to assessing
traditional serum RV-specific IgA and stool RV shedding after immunization (Aim 1). We will characterize gut
microbial composition and function using metagenomic sequencing at multiple pre-vaccination time points in
vaccine responders and nonresponders to determine if the abundance of B. longum and capacity to synthesize
folate predict vaccine immunogenicity (Aim 2). We will analyze the metabolic byproducts to identify if folate or
other metabolites enhance vaccine response (Aim 3). Our unique team of experts in vaccinology, immunology,
microbiology, biochemistry, and bioinformatics will ensure successful integrative analysis and interpretation of
these immunologic and multi-omics data. Completion of the study will provide a comprehensive
characterization of microbial and metabolic biomarkers of RV vaccine responses, paving the way for targeted
immune augmentation strategies.

## Key facts

- **NIH application ID:** 10923733
- **Project number:** 7R01HD100542-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Pia S Pannaraj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $551,221
- **Award type:** 7
- **Project period:** 2023-09-07 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923733

## Citation

> US National Institutes of Health, RePORTER application 10923733, Gut microbial and metabolic mediators of rotavirus vaccine response (7R01HD100542-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10923733. Licensed CC0.

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