# Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma

> **NIH NIH U19** · BOSTON CHILDREN'S HOSPITAL · 2022 · $198,606

## Abstract

Project Summary – Project 3 (PR3)
 Immune development in early life (IDEAL) is dynamic and growing evidence suggests that it impacts the
risk for common undesirable clinical phenotypes including low vaccine responsiveness, and proneness to
respiratory infection and/or asthma. However, little is known regarding precise mechanisms nor how to redirect
immune development to more favorable phenotypes. The Precision Vaccines Program (PVP) at Boston Children’s
Hospital (BCH) has developed cutting-edge human in vitro assays which model age related changes in leukocyte
function- i.e., immune ontogeny and population (e.g. age)-specific effects and mechanisms of action of
immunomodulatory agents, including metabolites, proteins, adjuvants and vaccines.
 Project 3 (PR3) will leverage human in vitro modeling to gain insight into signaling pathways that are
relevant to the clinical phenotypes observed. Our published and unpublished preliminary data indicate that our
sample-sparing human in vitro assay platforms can model innate and adaptive immune responses of infants and
young children which vary by age and disease status. Our hypothesis is that our innate and adaptive in vitro
modeling platforms can meaningfully interrogate molecular signaling pathways relevant to endotypes
(disease sub-types) of clinical phenotypes such as vaccine responsiveness, respiratory infection and/or
asthma. Our goal is to leverage our cutting-edge human in vitro assay systems to model human immune cell
responses to infant vaccines as well as to confirm, assess and translate the pathways identified in PR1 and PR
2. We will achieve this goal by pursuing the following Specific Aims (SAs): SA1. Assess mechanisms
underlying IDEAL endotypes. In this aim we will pursue molecular interrogation of pathways, biomarkers,
metabolites discovered in PR1 and PR2. SA2. Identify immunomodulators that re-direct trajectories from
unfavorable to favorable endotypes. We will model immune activation in response to agents capable of re-
shaping immune endotypes, including agents that impact the relevant endotype-associated pathways identified
in PR1 and PR2 .
 Overall, successful completion of PR3 will provide fresh insight into IDEAL in relation to vaccine
responsiveness, infection and/or asthma proneness. This effort will provide mechanistic insight into IDEAL, help
confirm and probe novel prognostic biomarkers and pathways identified in PR1 and PR2, and identify agents (e.g.,
proteins, metabolites, adjuvants, vaccines) that can redirect human infant leukocytes away from unfavorable
endotypes associated with low vaccine responsiveness, respiratory infection and/or asthma and towards favorable
trajectories and endotypes thereby advancing child health.

## Key facts

- **NIH application ID:** 10435043
- **Project number:** 1U19AI168643-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** OFER LEVY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,606
- **Award type:** 1
- **Project period:** 2022-03-10 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435043

## Citation

> US National Institutes of Health, RePORTER application 10435043, Project 3: In vitro modeling to define mechanisms of childhood vaccine response, susceptibility to respiratory infectious disease and asthma (1U19AI168643-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10435043. Licensed CC0.

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