Blocking Respiratory Syncytial Virus infection utilizing decoy ICAM-1 receptor proteins

Abstract Respiratory syncytial virus (RSV) infections result in a significant number of hospitalizations for young children and the elderly each year, and current infection rates continue to rise, leading to a substantial public health burden. While numerous vaccine candidates are in clinical trials, there is currently no approved RSV vaccine to prevent infection or antiviral treatment after infection. There is an urgent need to find new therapeutics and strategies that reduce severe RSV disease that could improve health and save lives. The RSV fusion (F) protein is critical for binding host cells and mediating infection and is the target of most candidate vaccines. The RSV F protein has been shown to interact with several host-cell surface receptor proteins such as Intercellular Adhesion Molecule 1 (ICAM-1), NCL, EGFR, IGF1R, and infect respiratory epithelial cells. In this study, we confirmed ICAM-1 could bind RSV F protein and inhibit RSV infection via an RSV neutralization assay. Using RSV F protein as bait, we immunoprecipitated RSV F interacting proteins from A549 respiratory cells and performed mass spectrometry analysis to identify novel host proteins that bind RSV F protein. Finally, we engineered a mRNA-lipid nanoparticle (LNP) expressing soluble ICAM-1. The goal is to utilize the ICAM-1 mRNA-LNP as a passive intranasal vaccine that would result in over-expressed soluble ICAM-1 in respiratory mucosal surfaces to function as a decoy receptor that would reduce RSV infection. We are evaluating this therapeutic approach in preclinical models as a prophylactic or treatment after infection. ICAM-1 mRNA-LNP may provide a novel defensive strategy to reduce RSV infection or disease severity and augment future RSV vaccines that become approved. Children’s Mercy Research Partners