# Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

> **NIH NIH U01** · UNIVERSITY OF VIRGINIA · 2020 · $622,367

## Abstract

SUMMARY
We aim to understand the nature of CD4+ T cells that protect against rhinovirus (RV) infection. Rhinovirus
infection is a major cause of common cold and an important trigger of disease exacerbations among those
suffering from chronic lung disorders, thereby presenting an enormous health burden to society. The
knowledge gained in this project could inform the design of vaccines to prevent repeat infections and their
adverse sequelae, thereby greatly impacting human health. A major challenge is to identify those CD4+ T cells
that protect against the numerous different strains of RV. Our preliminary findings suggest that circulating RV-
specific CD4+ T cells directed against highly conserved regions of RV capsid proteins (VP1 and VP2) protect
against infection. These cells comprise a mixture of memory effector T-cell (Teff, CXCR5neg) and T follicular
helper (Tfh, CXCR5+) populations that we predict will mediate viral clearance (Teff), and promote antibody
production by B cells (Tfh). Here, we address the hypothesis that RV-specific Teff and Tfh cells recognizing
conserved RV epitopes confer cross-protection against RV strains through maintenance of stable lineage
commitment and function. In Aim 1, we will confirm that virus-specific Teff and Tfh cells induced during the
effector phase of RV infection persist into the memory phase and maintain their T-cell lineage relationships. To
accomplish this objective, novel MHCII tetramers displaying conserved RV-16 peptides will be used to monitor
the emergence and evolution of circulating RV-16-specific T cells in healthy adults who receive experimental
challenge with RV-16. High-dimensional immunophenotyping will be performed using mass cytometry coupled
with advanced computational tools to visualize and track discrete RV-specific T-cell populations, as well as
synchronized fluxes in B-cell populations and other cell types including CD8+ T cells, T cells, NK cells, and
NKT cells. Gene expression profiling, including single-cell transcriptomics, will be integrated to test whether
the degree of homogeneity within RV-specific T-cell populations is preserved into the memory phase. In Aim 2,
the capacity for pre-existing RV-16-specific T-cell populations induced by primary exposure to protect against
re-infection with the heterotypic strain RV-39, will be addressed using a novel sequential RV challenge model
that involves re-challenge with either RV-16 or RV-39 four months after RV-16 exposure. The relationship
between higher numbers of pre-existing RV-16-specific T cells and correlates of protection against RV-39,
including quantitative viral shedding and production of cross-reactive serum antibodies, will be determined.
Further, we will explore how homotypic and heterotypic secondary viral exposures modulate T-cell populations
with protective attributes. Finally, using in vitro assays, we will confirm that Teff and Tfh cells that persist after
primary and secondary RV exposures can exert cross-protecti...

## Key facts

- **NIH application ID:** 9938404
- **Project number:** 5U01AI125056-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Judith A Woodfolk
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $622,367
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938404

## Citation

> US National Institutes of Health, RePORTER application 9938404, Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans (5U01AI125056-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938404. Licensed CC0.

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