# Project 2

> **NIH NIH U19** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $687,394

## Abstract

ABSTRACT
Infants and young children are at higher risk for severe manifestations of certain respiratory viruses, such as
influenza and RSV, compared to older children or adults. Interestingly, SARS-CoV-2 infection has shown the
opposite trend, with infants being at lower risk of serious outcomes. The molecular and cellular mechanisms
underpinning vulnerability to some infections and protection from others are poorly understood, but intrinsic
properties of the post-natal immune system might be at their core. Systems biology tools can resolve these
knowledge gaps through detailed analysis of the transcriptome, epigenome and function of immune cell
populations across the life span. This project capitalizes on our experience in studying the human immune
system through childhood in health and disease, and the availability of immune monitoring assays for use with
small-volume samples. Recently, we have leveraged innovative technologies, i.e., ATAC-seq for assessing
chromatin accessibility, RNA-seq, high-definition cellular immunophenotyping at the bulk and single cell levels
as well as custom-built integrative analysis pipelines. Our preliminary data confirm that we can maximally
leverage infant samples to capture transcriptional and regulatory genome-wide signatures associated with the
developing immune system in response to viral infections and vaccination with unprecedented granularity.
We propose to assess the immune responses to infection with two viruses, influenza and SARS-CoV-2,
occurring in the first six months of life by leveraging our immune profiling platform. We will track age-related
changes in immune cell composition, transcriptome and epigenome during this first encounter with the virus
and will subsequently monitor these parameters upon vaccination against these viruses yearly for a period of
three years. Aim 1 will define the phenotype/cell composition, transcriptome and epigenome of infant PBMCs
upon their first encounter with either Influenza or SARS-CoV-2 viruses. Aim 2 will Characterize the PBMC
phenotype/cell composition, transcriptome and epigenome in response to vaccination against influenza and
SARS-CoV-2.

## Key facts

- **NIH application ID:** 10862559
- **Project number:** 5U19AI168632-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Maria Virginia Pascual
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $687,394
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862559

## Citation

> US National Institutes of Health, RePORTER application 10862559, Project 2 (5U19AI168632-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10862559. Licensed CC0.

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