# Elucidating Mechanisms of Mucosal Immune Protection Against Respiratory Syncytial Virus in Infants

> **NIH NIH R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2024 · $575,767

## Abstract

PROJECT SUMMARY/ABSTRACT:
Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract viral infection in infants
and is responsible for ~60,000 in-hospital deaths annually, with most deaths occurring in infants less than
three months of age. Reinfections are common, and those who develop severe bronchiolitis are at further risk
of developing chronic lung diseases such as asthma. Past efforts to prevent RSV infection in infants through
vaccination with formalin-inactivated virus were disastrous resulting in 80% of vaccinees being hospitalized
following community-acquired RSV infection. This has hampered RSV vaccine development for nearly 50
years. We, and other researchers, have used neonatal (i.e., <7d of age) mouse models of RSV infection to
mimic the disease in human infants. Recently, we have shown that type I interferon (IFN-I) responses are
deficient in neonatal mice, which is consistent with findings in human infants. As repeated infections are
indicative of insufficient adaptive immunity, we assessed antibody responses and demonstrated that,
congruent with deficiencies in IFN-I, neonatal mice and infants fail to produce RSV-specific IgA. We identified a
mechanistic relationship between these components by demonstrating that IgA production requires IFNα in
mice. This is especially important, because RSV-specific IgA responses correlate significantly with protection
from disease and, in contrast to adults, infants and neonatal mice fail to mount such responses upon infection.
IFNα administration in neonatal mice induced RSV-specific IgA production and decreased RSV disease
severity. Importantly, neonatal B regulatory lymphocytes (nBregs) expressing IL10, but not IgA, have been
observed in RSV-infected infants and neonatal mice in a time-frame consistent with decreased IFN-I levels.
Together, these findings guide our hypothesis that failure to develop protective IgA responses in the
respiratory mucosa is responsible for RSV severity. We will explore the validity of this hypothesis using
unique sample sets from human infant RSV infection cohorts and age-relevant mouse models with three
specific aims. Aim 1 will demonstrate that the inability of infants to induce mucosal RSV-specific IgA in
response to RSV infection is responsible for enhanced disease severity. Aim 2 will determine whether failure to
induce BAFF/APRIL hinders the development of IgA responses to RSV in infants. Aim 3 will establish that
nBregs suppress RSV-specific IgA production in infants. The idea that age-dependent regulation of type I IFN
regulates the development of protective IgA responses in the respiratory mucosa following RSV infection is
novel. We will employ innovative methodologies including single-cell RNAseq (scRNASeq) on B-cell subsets in
samples from RSV-infected infants and spatial transcriptomics in samples from RSV-infected neonatal mice to
characterize Breg phenotypes, transcriptional programs, and local functions. Data derived from ...

## Key facts

- **NIH application ID:** 10906098
- **Project number:** 5R01AI090059-13
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Stephania A Cormier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $575,767
- **Award type:** 5
- **Project period:** 2011-08-11 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906098

## Citation

> US National Institutes of Health, RePORTER application 10906098, Elucidating Mechanisms of Mucosal Immune Protection Against Respiratory Syncytial Virus in Infants (5R01AI090059-13). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10906098. Licensed CC0.

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