# High Precision System Analysis of Infant Immune Responses

> **NIH NIH U01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2021 · $1,258,393

## Abstract

PROJECT SUMMARY
This project seeks to surmount current limitations in our understanding of early infant immunity
through longitudinal genomic and cellular studies of immune development and primary responses to
routine two-month vaccines. Infants and young children are more susceptible to invasive infections than
adults owing to overall reduced competency of protective immune responses, including to vaccines, which
require administration of multiple doses over several months for adequate long-term protection. While
immunization programs have dramatically decreased the global morbidity and mortality caused by infections, it
remains that infectious diseases are the most frequent cause of death in infants and young children. The
cellular, molecular and genomic mechanisms that contribute to this vulnerability are largely unknown. Ever
more powerful tools in genomics and systems biology offer exciting opportunities to resolve these knowledge
gaps through detailed analysis of the transcriptomic, epigenomic and functional signatures of infant immune
cell populations. However, such studies have been limited by the difficulty in accessing clinical samples from
infants, the incompatibility of many genomic technologies for use in small-volume samples, and the lack of
bioinformatic tools for integrating and interpreting complimentary yet complex datasets. This proposal will
capitalize on our experience studying the infant immune response, our access to infant populations, and our
expertise in developing immunogenomic assays for use in human blood-derived immune cells (PBMCs).
Specifically, we propose a longitudinal analysis of PBMCs from infants i) at 2, 6 and 12 months, to establish
the baseline cellular, phenotypic and genomic signatures of immune development (Aim 1), and ii) at key time
points over the course of routine two-month vaccinations, to identify the cellular, phenotypic and genomic
signatures associated with primary immune responses to vaccines (Aim 2). We will use an innovative
immunogenomic Profiling and Analysis Pipeline (iPAP) we developed that allows us to extract maximal
transcriptomic (RNA-seq), epigenomic (ATAC-seq), isoformic (SMRT-seq), cytometric (50-parameter flow
cytometry) and immunophenotypic (CyTOF) information from a single infant blood sample, and to integrate
these distinct datasets for unparalleled depth of insight into the correlated cellular and genomic signatures of
immune development and vaccine responsiveness. Our approach is unbiased, multifaceted and highly
technology-driven, combining many of the most cutting-edge genomic and quantitative cell-based technologies
with our deep experience in applying these technologies for use in human infant immune cells. In line with the
goals of this RFA, this project will yield a comprehensive dataset from infants that can be used to
identify fundamental mechanisms and pathways associated with immune development and primary
responses to vaccines, and will set the stage for future stu...

## Key facts

- **NIH application ID:** 10267402
- **Project number:** 3U01AI131386-05S1
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Octavio Ramilo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,258,393
- **Award type:** 3
- **Project period:** 2020-06-18 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267402

## Citation

> US National Institutes of Health, RePORTER application 10267402, High Precision System Analysis of Infant Immune Responses (3U01AI131386-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10267402. Licensed CC0.

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