Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory illness in infants and young children worldwide, making it a high priority for development of strategies for prevention and treatment. RSV can cause repeat infections throughout life, with serious complications in elderly and immunocompromised patients. Previous studies indicate that the RSV G protein binds through a CX3C chemokine motif to the host chemokine receptor, CX3CR1, and modulates the inflammatory immune response. In the current study, we examined the contribution of CX3CR1 to the immune response to RSV infection in mice. CX3CR1-deficient mice showed an impaired innate immune response to RSV infection, characterized by substantially decreased NK1.1(+) natural killer, CD11b(+), and RB6-8C5(+) polymorphonuclear cell trafficking to the lung and reduced IFNgamma production compared with those in wildtype control mice. Leukocytes from CX3CR1-deficient mice were poorly chemotactic toward RSV G protein and CX3CL1. These results substantiate the importance of the RSV G CX3C-CX3CR1 interaction in the innate immune response to RSV infection.

We examined whether prophylactically administered anti-RSV G monoclonal antibody (mAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated (FI-RSV) enhanced disease in mice. mAb 131-2G administration one day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')2 forms of mAb 131-2G mAB administered one day prior to infection in FI-RSV vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein mAb might provide prophylaxis against both primary infection and FI-RSV associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of non-live virus vaccines.