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

Complete protection against respiratory syncytial virus (RSV) infection was induced in mice vaccinated on two occasions with 2.5 mug of DNA, encoding the fusion (F) protein of RSV, precipitated onto gold microbeads. In contra st, immunisation with DNA encoding the attachment (G) protein of RSV result ed in a significant reduction in viral load following infection, but did no t afford complete protection. Gene gun delivery of DNA-F elicited a T helpe r-2 (Th2) biased immune response that could not be modulated by the co-deli very of plasmids encoding IL-2, IL-12 or IFN gamma. Similarly gene gun deli very of DNA-G primed a Th2 response. Thus, all gene gun vaccinated mice pro duced a predominant Th2 biased pulmonary immune response characterised by t he production of IL-4 and IL-5 with little IFN gamma following RSV challeng e. Analysis of bronchoalveolar lavage (BAL) cells, 5 days post challenge, i ndicated that there was only a two-fold increase in the number of inflammat ory cells in vaccinated compared with control animals. Despite the strong T h2 cytokine bias of lung lymphocytes and the predominant recruitment of CD4 (+) T cells, following challenge, there was not a marked pulmonary eosinoph ilic response (range from 2 to 7% of BAL). In contrast, the BAL from mice v accinated with control plasmid contained significantly more eosinophils tha n any other group. (C) 2000 Elsevier Science Ltd. All rights reserved.