RSV is the leading cause of bronchiolitis, viral pneumonia, and viral death in infants. RSV is the leading cause of respiratory failure and mechanical ventilation in infants. There is no RSV vaccine in use and no widely available therapies. RSV is not only a scourge of infancy but also a major cause of asthma exacerbations in children and adults, and a major cause of pneumonia in the elderly. Airway mucus is a hallmark feature of RSV lower respiratory tract infection. Mucus, necrotic epithelial cell debris, and inflammatory cells obstruct the airways, leading to characteristic wheezing and respiratory failure in severe cases. We identified and derived strains of RSV that exhibit differential disease phenotypes in mice. Some RSV strains induce high levels of the cytokine IL-13, airway mucus, severe histopathology, and pulmonary obstruction, whereas other strains induce a more protective TH1-type response. 

HRV and RSV are the leading causes of the common cold.  Each presents different challenges for a safe and effective vaccine.  We are working to bring several vaccine candidates through clinical trials, in addition to researching new vaccine candidates and methods.  This pairs well with the second main aim of my lab, to define mechanisms of RSV immunopathogenesis and investigate the role of RSV strain differences in differential RSV pathophysiology. 

We use differentially virulent RSV strains, and a novel RSV reverse genetics system we developed, to dissect molecular mechanisms leading to airway mucus expression, bronchiolitis, and pulmonary obstruction in the mouse model. These studies led to our current vaccine candidates, and will hopefully lead to additional effective vaccines  and/or therapies for RSV disease.    A comprehensive understanding of how RSV strain differences affect pathogenesis and immunity will require bridging gaps between basic research, epidemiology, and clinical studies.