Chitosan is a
polysaccharide capable of augmenting immune responses with a proven safety record in animals and humans. These properties make it a potentially attractive agent for the prevention and treatment of
infectious disease.
Infection by respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory disease in young children throughout the world. There is no licensed
vaccine available against RSV whereas
inactivated vaccine is known to cause enhanced respiratory disease instead of protection. Here, we investigated whether
chitosan administered one or three days post-
infection could protect animals against
RSV infection and whether it could alter immune responses or immunopathology induced by inactivated
RSV vaccine when administered twice before
RSV infection. We found
chitosan could modestly protect animals against
RSV infection when given post-
infection, while, in conjunction with inactivated
RSV vaccine when given pre-
infection, it could significantly reduce
RSV infection in mice. Further mechanistic investigation revealed that
chitosan enhanced
antigen-specific immune responses through augmenting the induction of regulatory T cells, lung resident T cells and
neutralizing antibodies while reversing Th2-skewed immune responses induced by inactivated
RSV vaccine but, surprisingly, failing to reverse lung histopathology. Overall, this study sheds more light on the molecular mechanisms underlying inactivated
RSV vaccine-induced disease.