Th2-independent development of vaccine-enhanced disease associated with formalin-inactivated respiratory syncytial virus immunization (P3182)

Abstract

Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and there is currently no licensed RSV vaccine. Children immunized with a formalin-inactivated (FI) RSV vaccine during the 1960's exhibited exacerbated disease and increased mortality following a natural RSV infection. It is widely believed that a Th2-biased response directly contributes to the lung injury associated with FI-RSV vaccine-enhanced disease. This is in part due to the emphasis placed on the development of pulmonary eosinophilia noted in the autopsy reports from the FI-RSV vaccine trials. Furthermore, RSV challenge of FI-RSV-immunized mice results in extensive pulmonary inflammation including increased numbers of eosinophils and Th2 cytokine producing CD4 T cells. Depletion of CD4 T cells significantly ameliorates both airway resistance and weight loss associated with FI-RSV vaccine-enhanced disease. However, FI-RSV-immunized BALB/c mice genetically deficient in eosinophils elicit similar airway resistance, weight loss, and histopathology as compared to wild-type controls following RSV challenge. Moreover, FI-RSV-immunized STAT6-deficient mice exhibit significantly reduced Th2-associated responses, but similar airway resistance and weight loss as compared to wild-type controls following RSV challenge. Our results indicate that Th2 responses do not significantly contribute to critical disease parameters associated with FI-RSV vaccine-enhanced disease.