Biology subjects

Ghosn, J.

Publications and source records attributed to Ghosn, J..

2 recordsLinked to original sources

bioRxiv2025

Identification and Functional Characterization of Regulatory Variants in DPP9 Associated with COVID-19 Severity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a wide-range of clinical outcomes, which have been extensively studied through genome-wide association studies (GWAS). Starting from lead genetic variants associated with COVID-19 infection and severity, we identified a subset of non-coding candidate variants with potential regulatory functions. Using bioinformatics analysis and functional screening in three cell lines, we prioritized two DPP9 variants within a haplotype that increases the risk of severe COVID-19. This haplotype exhibited increased regulatory activity and altered transcription factor binding, suggesting its role in influencing COVID-19 severity through modulation of DPP9 expression in immune and lung cell types. The interest of our study lies in the functional characterization of regulatory variants responsible for the higher levels of DPP9 and lung damage observed in patients with severe COVID-19. These findings advance our understanding of genetic risk factors for COVID-19 and highlight functional SNPs that may guide future therapeutic research.

genetics↗

bioRxiv2021

Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

The emergence of SARS-CoV-2 variants of concern (VOCs) that escape pre-existing antibody neutralizing responses increases the need for vaccines that target conserved epitopes and induce cross-reactive B- and T-cell responses. We used a computational approach and sequence alignment analysis to design a new-generation subunit vaccine targeting conserved sarbecovirus B- and T-cell epitopes from Spike (S) and Nucleocapsid (N) to antigen-presenting cells expressing CD40 (CD40.CoV2). We demonstrate the potency of CD40.CoV2 to elicit high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with improved viral control and survival after challenge. In addition, we demonstrate the potency of CD40.CoV2 in vitro to recall human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes. Overall, these findings provide a framework for a pan-sarbecovirus vaccine.

immunology↗