Respiratory syncytial virus infection of gene gun vaccinated mice induces Th2-driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein

Abstract

Complete protection against respiratory syncytial virus (RSV) infection was induced in mice vaccinated on two occasions with 2.5 μg of DNA, encoding the fusion (F) protein of RSV, precipitated onto gold microbeads. In contrast, immunisation with DNA encoding the attachment (G) protein of RSV resulted in a significant reduction in viral load following infection, but did not afford complete protection. Gene gun delivery of DNA-F elicited a T helper-2 (Th2) biased immune response that could not be modulated by the co-delivery of plasmids encoding IL-2, IL-12 or IFNγ. Similarly gene gun delivery of DNA-G primed a Th2 response. Thus, all gene gun vaccinated mice produced a predominant Th2 biased pulmonary immune response characterised by the production of IL-4 and IL-5 with little IFNγ following RSV challenge. Analysis of bronchoalveolar lavage (BAL) cells, 5 days post challenge, indicated that there was only a two-fold increase in the number of inflammatory cells in vaccinated compared with control animals. Despite the strong Th2 cytokine bias of lung lymphocytes and the predominant recruitment of CD4 + T cells, following challenge, there was not a marked pulmonary eosinophilic response (range from 2 to 7% of BAL). In contrast, the BAL from mice vaccinated with control plasmid contained significantly more eosinophils than any other group.