# Project 1

> **NIH NIH U19** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $486,580

## Abstract

ABSTRACT
Viral respiratory infections are responsible for major morbidity and mortality in early life. Infants account for a
significant proportion of influenza hospitalizations and are considered a top high-risk group. In addition to the
acute morbidity, initial immune responses to influenza shape/imprint the immune system and affect subsequent
responses to influenza infections and vaccinations, which tend to induce humoral responses skewed towards
epitopes present in the first influenza antigen encountered. In contrast, SARS-CoV-2 infection in infants is
generally mild and less severe than in older individuals. This is remarkable and suggests that there are unique
features on how the infant immune system responds to SARS-CoV-2, compared to its responses against other
respiratory viruses, that can be leveraged to improve our understanding of early life immunity.
On the basis of these observations, we hypothesize that early life viral respiratory infections elicit virus-specific
immune responses that lead to distinct immune developmental trajectories. To address this hypothesis, we
will compare three longitudinal cohorts: i) infants infected with SARS-CoV-2; ii) infants infected with influenza
virus; and as reference iii) healthy infants with none of those two infections. After the acute infections, children
will be followed longitudinally for three years and immune responses assessed in the context of influenza and
COVID-19 vaccinations.
We designed the following specific aims: Aim 1. Define the differences of blood transcriptional immune
signatures in infants with SARS-CoV-2 versus infants with influenza infection. We will assess the differences in
immune signatures between: i) the two acute viral infections SARS-CoV-2 versus influenza in infants; ii) primary
acute infection versus primary vaccination, and iii) between initial (primary responses) and subsequent
vaccinations (recall responses). Will correlate immune signatures with antibody profiles and B cell responses.
Aim 2. Define the magnitude, immunodominance pattern and breath of the antibody responses to influenza virus
and evolution of antibody responses to SARS-CoV-2. First, we will define the evolution of the antibody responses
to influenza virus in infants upon initial infection and subsequent vaccination(s). Second, we will define the
antibody responses to SARS-CoV-2 in infants upon initial infection and subsequent vaccination(s). Additionally,
we will compare primary immune responses to infection versus vaccination with each of the two viruses. Aim
3. High-throughput longitudinal evaluation of B cell responses to influenza and SARS-CoV-2. We will perform
high-throughput single cell assays using the 10xGenomics drop-seq platform to perform multi-variate analyses
of single B cells at the level of the variable gene repertoire, cell-surface phenotype, transcriptome, and Ig
specificity.

## Key facts

- **NIH application ID:** 10862558
- **Project number:** 5U19AI168632-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Octavio Ramilo
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $486,580
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862558

## Citation

> US National Institutes of Health, RePORTER application 10862558, Project 1 (5U19AI168632-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862558. Licensed CC0.

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