Mechanism of lung injury in cotton rats immunized with formalin-inactivated respiratory syncytial virus

Respiratory syncytial virus (RSV) seronegative cotton rats were immunized intramuscularly at four and eight weeks of age with either formalin-inactivated, alum-precipitated RSV grown in HEp-2 cell tissue cultures or virus-free HEp-2 cell tissue cultures similarly prepared. Sham-immunized animals served as controls. At 12 weeks of age, all animals were challenged with 6 × 10⁵ plaque forming units of live RSV via the intranasal route. Animals were killed at predetermined days and evaluated for RSV antibody, virus replication and pulmonary histopathology. Of animals immunized with inactivated-RSV, 88% developed neutralizing antibody to RSV. Virus replication in the lungs of such animals was significantly reduced compared with tissue-culture-immunized animals. Surprisingly, however, both groups exhibited pulmonary histopathology, characterized by polymorphonuclear and mononuclear interstitial infiltrates. The virus-immunized animals manifested a more severe inflammatory reaction that reached a peak earlier than the virus-free, tissue-culture-immunized control group. In contrast, sham-immunized animals, when infected with live RSV for the first time, developed little or no pulmonary histopathology. The data suggest that the pathogenesis of pulmonary injury during natural RSV infection in the immunized host is due primarily to prior sensitization to the virus. In the animal model, sensitization to non-viral tissue culture components also contributes to lung injury.