# Human Airway Biomimetics for RSV and Other Respiratory Viruses

> **NIH NIH U19** · BAYLOR COLLEGE OF MEDICINE · 2022 · $348,710

## Abstract

PROJECT SUMMARY – Project 2
Respiratory syncytial virus (RSV) is a major global respiratory pathogen. The Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has resulted in an unprecedented crisis. Respiratory virus
infections are often accompanied by gastrointestinal (GI) symptoms, but how respiratory pathogens cause GI
disease is not understood. Moreover, a number of vaccines and therapeutics are being developed against these
important pathogens, however, the existing models do not recapitulate the human experience. Small animal and
non-human primate models fall short of mimicking human disease, and the human RSV challenge model is
expensive and raises safety concerns. The requirement for BSL-3 facilities to study SARS-CoV-2 hampers data
generation and increases cost. The human endemic CoV-NL63 can serve as a proxy for SARS-CoV-2 because
it uses the same host receptor, angiotensin-converting enzyme 2. This project will develop an ex-vivo Human
Challenge Airway Model by advancing our current 3-dimensional (3D) nose/lung model for studies on
RSV and CoV-NL63 (proxy for SARS-CoV-2) to address the urgent need for a preclinical model that
recapitulates the human disease. In collaboration with the Human Biomimetic Scientific Core, we have
developed the expertise for isolating stems cells and generating 3D nose and lung organoid lines from nasal
wash and bronchoalveolar fluids, respectively. Our internationally recognized expertise in RSV and other
respiratory viruses uniquely positions us to develop advanced 3D nose/lung models for dissecting the
pathogenesis of RSV (Aim 1), and develop airway and GI platforms with the Engineering Micro-Environment
Core (EMEC) to evaluate molecular mechanisms driving the lung-gut axis of respiratory virus disease (Aim 2).
We will select donors based on sex and age so that we can comprehensively study the complex interactions of
host (age, sex, distinct airway sites, and immune cells) and virus, and the contribution of humoral and cellular
immune responses in an HLA-restricted system. We will also evaluate the lung-gut axis by studying the
downstream effects of RSV and CoV-NL63 airway infection on the GI tract by either direct (infection) or indirect
(inflammation) pathways using lung-gut flow systems. This project is responsive to the RFA by the development
of an advanced nose/lung model with increased complexity that includes humoral and cellular immunity, as well
as defining novel mechanistic pathways in the lung-gut axis of respiratory virus disease. The global scientific
community will benefit immensely from a 3-D nose/lung airway-virus model that recapitulates human virus
infection and serves as a platform to evaluate therapeutics and vaccines.

## Key facts

- **NIH application ID:** 10462792
- **Project number:** 5U19AI116497-07
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Pedro A Piedra
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $348,710
- **Award type:** 5
- **Project period:** 2015-03-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462792

## Citation

> US National Institutes of Health, RePORTER application 10462792, Human Airway Biomimetics for RSV and Other Respiratory Viruses (5U19AI116497-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10462792. Licensed CC0.

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