# COVID-19 Supplement: Systems Immune Profiling of Divergent Responses to Infection

> **NIH NIH U19** · YALE UNIVERSITY · 2021 · $642,765

## Abstract

The overall goal of the Human Immunology Project Consortium (HIPC) program is to capitalize on recent
advances in immune profiling methods in order to create a novel public resource that characterizes diverse
states of the human immune system. We propose to contribute to this program through deep
interrogation and a broad systems approach that will identify molecular signatures of divergent
human immune responses to infections. The three projects that comprise our U19 each leverage a
common experimental infrastructure to focus on a different infectious diseases: the Lyme disease
spirochete Borrelia burgdorferi, emerging arthropod-borne West Nile virus, and effects of aging on
vaccination against influenza. Our goal is to delineate human immune signatures that are associated with
the divergent manifestations in the population, using well-defined patient cohorts and a multidimensional
analytical approach to quantitatively assess primary human immune cell function. Our program employs
cutting-edge immune profiling such as multidimensional profiling by CyTOF, metabolomics, nanoscale
technologies such as MuSIC (MultiSpectral Imaging Cytometry), and RNA-seq on single cells that will
inform a systems approach to elucidate the biologic signatures defining immune responsiveness.
Commonalities between the responses in different tissues, and to the different infection types, will be
determined by quantifying signature enrichments, and by identifying conserved active sub-networks in this
immune-specific functional network.
This collaborative U19 takes advantage of enormous strengths across our institutions to tackle a
challenging issue in human immunology. The investigators in this proposal have established collaborations,
regular interactions, and a track record of shared success. Our three research projects are supported by
shared cores for Administration, Data Management and Analysis, Single Cell Immunophenotyping, and
Clinical Recruitment. The united goal of these varied approaches is to define elements of the immune
response that contribute to divergent infection outcomes. This multifactorial, wide-angle view of the immune
response will be compiled employing the expertise of each individual approach for Systems Modeling from
deep interrogation of three sets of stratified patient cohorts. The output of this functional systems
immunology approach will be definitions of human immune signatures following multiple forms of infectious
challenges with the ultimate goal of defining future targets for intervention and predicting susceptibility or
resistance.

## Key facts

- **NIH application ID:** 10265708
- **Project number:** 3U19AI089992-10S3
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** David A. Hafler
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $642,765
- **Award type:** 3
- **Project period:** 2020-05-18 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265708

## Citation

> US National Institutes of Health, RePORTER application 10265708, COVID-19 Supplement: Systems Immune Profiling of Divergent Responses to Infection (3U19AI089992-10S3). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10265708. Licensed CC0.

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