'FROM DISCOVERY TO RECOVERY'
My current research focuses on two principle but interrelated topics, the immunopathogenesis of respiratory syncytial virus (RSV) and the development of Sendai virus (SeV) as a vector.
RSV is the principle cause of severe lung disease in young infants. It is also associated with significant morbidity and mortality in the elderly and immunocompromised individuals. Despite its medical importance there are no vaccines or therapeutics available. Importantly, RSV infection does not lead to efficient longterm immune memory responses and re-infections are common throughout life. The mechanisms by which RSV causes disease are unclear, as are the means by which it circumvents the induction of immune memory. My group is currently developing unique ex-vivo/in-vitro models of RSV infection based on paediatric primary airway epithelial cells, the primary targets of RSV infection. In the simplest form, we exploit monolayers of primary epithelial cells. We have also developed the capacity to differentiate these cells into pseudo-stratified well-differentiated cultures that look and behave like respiratory epithelium in vivo. Both models provide important opportunities to study RSV/host interactions in physiologically relevant cultures. RSV also has the capacity to impede or circumvent innate and adaptive immune responses to infection, including type I interferon signalling and T cell proliferation. We are currently addressing these issues in appropriate in vitro and ex-vivo models.
SeV is a rodent virus and a close relative of human parainfluenza virus type 1 (hPIV1). Indeed, it has potential as a classical Jennerian vaccine against hPIV1. We have developed a reverse genetics system for SeV and have demonstrated the capacity to express heterologous genes from SeV, either as extra-numeral genes or bicistronic constructs in association with SeV genes. We are exploiting this technology to generate recombinant SeVs expressing either reporter genes or RSV antigens as a means to study SeV and RSV interactions with the immune system and ultimately generate novel vaccines against important respiratory viral pathogens.