# Viral and Host Determinants of Infant and Childhood Allergy and Asthma

> **NIH NIH U19** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $164,815

## Abstract

Abstract
The long term objective of this application is to define the relationship between infant respiratory syncytial virus
(RSV) infection and the host response that enables asthma inception. There is abundant evidence that
children who experience severe RSV bronchiolitis during infancy are at greater risk for developing asthma later
in childhood; however the viral and host determinants that lead to asthma development are not known. In
Project 1, we propose to extend longitudinal follow-up of the INSPIRE (Infant Susceptibility to Pulmonary
Infections and Asthma Following RSV Exposure) population based birth cohort of over 1,900 middle
Tennessee infants who will be age 4 years at the end of the first U19 funding period. This will enable us to
confirm if the RSV strains that we have identified to cause more severe infant morbidity and early wheezing
outcomes are also associated with asthma, and the pathways through which these RSV strains cause asthma.
We propose the following: (1) Identify RSV strains associated with asthma inception at ages 6 to 8 years; (2)
Determine how RSV strains impact the host microbial environment during primary RSV infection; (3) Assess
primary airway epithelial cell (AEC) response to asthma-causing RSV strains; (4) Determine RSV induced
immune responses associated with asthma inception in the INSPIRE cohort. In the first funding cycle we have
been the first group to ever sequence and identify RSV strains associated with significantly increased risk of
recurrent wheezing outcomes, as well as differential immune response and airway microbial patterns. We
found that infants infected with RSV strains that contained a mutation in the attachment (G) gene end
sequence (2stop-A4G mutation) had statistically significantly increased bronchiolitis severity scores compared
to infants infected with the RSV WT genotype. Infection with 2stop-A4G mutation strains is becoming
increasingly more common in human infants and studies from our group reveal that strains containing the
2stop-A4G mutation cause Th2 innate immune responses in mice and humans. In Project 2, we propose the
following in the mouse model of RSV infection: (1) determine the contribution of infection with RSV 2stop-A4G
to Th2 immunity in primary bronchiolitis, and (2) determine the contribution of 2stop-A4G to enhanced adaptive
immune responses to inhaled aeroallergen. Defining the contribution of specific RSV strains to infant
bronchiolitis and asthma pathogenesis highlights the clinical significance of our studies and may provide a
therapeutic target for vaccines and precision medicine approaches that focus on RSV mutations.

## Key facts

- **NIH application ID:** 10301919
- **Project number:** 3U19AI095227-11S2
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ray Stokes Peebles
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,815
- **Award type:** 3
- **Project period:** 2020-12-14 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301919

## Citation

> US National Institutes of Health, RePORTER application 10301919, Viral and Host Determinants of Infant and Childhood Allergy and Asthma (3U19AI095227-11S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10301919. Licensed CC0.

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