Abstract
BACKGROUND: Human rhinoviruses (HRVs) are the leading cause of upper respiratory tract infections, responsible for over half of all such infections. Infection rates among young children can reach as high as 8-12 episodes per year. While HRV infections typically result in mild common colds, they can also lead to more severe respiratory conditions, often in conjunction with bacterial coinfections. In addition, HRVs are implicated in the exacerbation of obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). T-cell responses play a crucial role in the immune defense against HRV. However, in patients with obstructive respiratory diseases, altered or dysregulated T-cell responses to HRV may not only fail to efficiently eliminate the virus but can also exacerbate inflammation and airway remodeling. Therefore, a deeper understanding of T-cell-mediated responses in the context of HRV infection, especially in vulnerable populations like those with COPD, is critical. It can provide new insights into mechanisms of both protection and disease exacerbation, potentially guiding the development of targeted therapies or vaccines that enhance protective immunity while minimizing harmful inflammation. OBJECTIVE: This study aims to (1) determine the population-wide coverage of HRV-specific T-cell responses, (2) characterize HRV-specific T-cell recall responses in disease cohorts compared to age-match healthy controls, and (3) identify biomarkers of protection and susceptibility within disease cohorts through a comparative analysis. METHODS: Participants with asthma and those with COPD, aged 5-15 and 40-70 years, respectively, will be recruited alongside healthy age-matched controls. Peripheral blood samples will be collected following informed consent from adult participants and from parents or guardians of minors, as applicable. Clinical, demographic, immunological, and genetic responses will be assessed both prior to and following in vitro stimulation with a pool of HRV-specific T-cell epitopes. Flow cytometry and functional assays will be used to analyze T-cell responses to HRV epitopes in the context of obstructive respiratory diseases. RESULTS: This study was funded in January 2023 by the Ministry of Science and Innovation of Spain. The primary aim of the study was achieved within the same year. Recruitment for the secondary and tertiary aims is currently ongoing. Preliminary findings highlight the potential significance of HRV-specific T-cell responses in individuals with asthma and those with COPD. A detailed characterization of these immune responses will provide critical insights into host-pathogen interactions and may serve as a foundation for the development of effective T-cell-based vaccines or immunotherapies targeting HRV. CONCLUSIONS: Here, we present an ethically approved study protocol for an observational and exploratory study investigating a novel epitope-based vaccine targeting HRV, with a focus on pediatric asthma and adult COPD cohort populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/73383.