Increased replication of respiratory syncytial virus (RSV) in pulmonary infiltrates is associated with enhanced histopathological disease in bonnet monkeys (Macaca radiata) pre-immunized with a formalin-inactivated RSV vaccine

The pathology of respiratory syncytial virus (RSV) disease in bonnet monkey s parallels findings with human RSV disease. RSV-infected animals pre-immun ized with a formalin-inactivated (FI) RSV vaccine develop inflammation in p eribronchiolar, perivascular, interstitial and intra-alveolar sites with lu ng inflammation scores significantly higher than animals with a primary RSV infection and those pre-immunized with an FI-Vero cell control vaccine (P = 0.05). Animals previously infected and re-exposed to RSV had significantl y lower alveolar, interstitial and total lung inflammation scores than in p rimary infection (P = 0.05). Immunization with two intra-muscular doses of 0.5 ml of the FI-RSV vaccine administered 21 days apart resulted in little serum-neutralizing and ELISA antibody, low levels of secretory IgA and a lo w lymphocyte proliferative response that was significantly lower than the r esponse observed in animals that were previously infected with live RSV. Hi gher RSV virus titres were detected in the lungs and lung lavage fluid of m onkeys immunized with the FI-RSV vaccine than in those with a primary infec tion (P = 0.001). RSV was detected by in situ hybridization in pulmonary in flammatory infiltrates, where the single most abundant infiltrating cellula r species was macrophages, so it may be these cells that support the enhanc ed virus replication that contributes to the enhanced pulmonary pathology o f FI-RSV immunization.