Understanding respiratory syncytial virus (RSV) vaccine-enhanced disease

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Abstract
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and children worldwide. In addition, RSV causes serious disease in elderly and immune compromised individuals. RSV infection of children previously immunized with a formalin-inactivated (FI)-RSV vaccine is associated with enhanced disease and pulmonary eosinophilia that is believed to be due to an exaggerated memory Th2 response. As a consequence, there is currently no licensed RSV vaccine and detailed studies directed towards prevention of vaccine-associated disease are a critical first step in the development of a safe and effective vaccine. The BALB/c mouse model of RSV infection faithfully mimics the human respiratory disease. Mice previously immunized with either FI-RSV or a recombinant vaccinia virus (vv) that expresses the attachment (G) glycoprotein exhibit extensive lung inflammation and injury, pulmonary eosinophilia, and enhanced disease following challenge RSV infection. CD4 T cells secreting Th2 cytokines are necessary for this response because their depletion eliminates eosinophilia. Intriguing recent studies have demonstrated that RSV-specific CD8 T cells can inhibit Th2-mediated pulmonary eosinophilia in vvG-primed mice by as yet unknown mechanisms. Information gained from the animal models will provide important information and novel approaches for the rational design of a safe and efficacious RSV vaccine.