Funding outcome

Respiratory Syncytial Virus (RSV) is a leading cause of infant hospitalization and death worldwide. In Canada, RSV is widespread in the community and accounts for 10-30% of clinical respiratory virus infections annually. Recently, two adult vaccines and a new preventative antibody have been approved for use, all of which target the RSV fusion protein (RSV-F). Given that viruses mutate to escape drug pressure, we must improve our understanding of RSV adaptation in response to therapeutics. Unfortunately, RSV whole genome sequence data is limited and there is a lack of research regarding clinical vs community circulating strains of RSV. Our lab found that in response to antibody pressure, RSV develops subtle resistance mutations in RSV-F that change the entire protein's shape, making it resistant to human and therapeutic antibodies. I am collecting nasal swabs from symptomatic participants to determine community circulating RSV strains. These are compared to clinical RSV provided to us by Alberta Precisions Laboratories to understand how RSV changes through the community and into the clinic. I am also investigating which sites in RSV-F are prone to mutation, with emphasis on sites targeted by therapeutics. Using computational modeling I can predict which mutations will change the protein structure and test them in an RSV model to evaluate their resistance to antibodies. Studies like as this are increasingly important given the novel RSV therapies in production. My work improves our understanding of RSV resistance mechanisms and viral surveillance strategies as a predictive tool that looks at community circulating RSV before it reaches vulnerable populations in the clinic.