Pathogenesis and vaccine development for respiratory syncytial virus and parainfluenzavirus-3

Morphometric determination of the extent of inflammation in the lungs of RSV-infected lambs

Project Team: Sylvia van den Hurk, Robert Brownlie, Laura Latimer, Amanda Galas-Wilson

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children, resulting in the hospitalization of ~2% of children in their first year of life. RSV is second to malaria as a cause of mortality due to a single pathogen in infants between 1 month and 1 year of age. Human parainfluenzaviruses (hPIVs) are second to RSV as causes of lower respiratory tract illness and hospitalization. Vaccines against RSV, hPIV3 and the related hPIV-1, 2, and 4 are not available but needed.

The factors that contribute to the severity of RSV disease in infants and elderly are not understood. We are studying age- and genetics-dependent differences in the clinical disease, lung pathology and innate and adaptive immune responses to RSV in animal models including mice, cotton rats and lambs.

We have developed a novel vaccine candidate for RSV that preclinical studies indicate is safe, effective, and induces long-lasting immune responses. The vaccine also induces robust immune responses in newborn animals, and is efficacious in the context of maternal immunization. The RSV vaccine is expected to enter phase 1 clinical trials in 2019.

The current focus is adding a PIV3 antigen to this vaccine, and testing the combination vaccine in various animal models. We are working on the mechanism of action of the vaccine components, as well as optimization for mucosal delivery.