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.
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