Subcellular site of expression and route of vaccination influence pulmonary eosinophilia following respiratory syncytial virus challenge in BALB/c mice sensitized to the attachment G protein

Abstract

The attachment glycoprotein (G) of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. Mutant cDNAs were constructed that encoded one or the other form of the protein and were expressed in recombinant vaccinia viruses (rVV). Mice were immunized with rVV by dermal scarification or i.p. injection to determine the contribution of the membrane-anchored and secreted forms of the G protein on the augmentation of pulmonary pathology seen following RSV challenge. Mice scarified with rVV expressing the membrane-anchored G protein had a markedly reduced pulmonary eosinophilic response following RSV challenge compared with mice scarified with rVV expressing either wild-type or secreted G protein. The induction of pulmonary eosinophilia in rVV-primed mice was also dependent upon the route of vaccination. An eosinophilic response was not observed in any groups of mice immunized i.p. with rVV expressing any of the different forms of the G protein. The difference in pulmonary pathology observed between dermal scarification or i.p. vaccinated mice was not reflected in a difference in cytokine production by splenocytes from vaccinated and challenged mice restimulated with RSV in vitro. Both groups produced significant levels of IL-4 and IL-5. These data suggest that the local APCs and lymphoid environment, together with the form of the G protein, influence pulmonary pathology following RSV challenge.