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Separation of pulmonary and systemic aspects of respiratory syncytial virus vaccine‐enhanced disease
Author(s) -
Castilow Elaine,
Varga Steven M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.857.20
Subject(s) - eosinophilia , immunology , vaccination , medicine , pneumovirinae , pulmonary eosinophilia , virus , stat4 , vaccinia , virology , biology , paramyxoviridae , recombinant dna , viral disease , signal transduction , stat , gene , asthma , biochemistry , stat3 , eosinophil
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in children. Prior vaccination with a formalin‐inactivated (FI) RSV vaccine resulted in enhanced morbidity and mortality upon natural RSV infection that was characterized by an extensive pulmonary mononuclear cell infiltrate and eosinophilia. Vaccination of BALB/c mice with a recombinant vaccinia virus expressing the attachment protein of RSV (vvG) results in pulmonary eosinophilia mimicking the response of the FI‐RSV vaccine recipients. The G protein elicits a CD4 T cell response that is comprised of a mixture of Th1 and Th2 cells which predominately express the VÎ 2 14 T cell receptor. We have utilized STAT6‐ and STAT4‐deficient mice to examine the role of IL‐4/IL‐13 and IL‐12 signaling in mediating individual aspects of RSV vaccine enhanced‐disease. We demonstrate that STAT6 is necessary for the development of pulmonary eosinophilia, but that systemic disease is unaltered in the absence of STAT6. In contrast, we find that STAT4 is necessary for systemic disease but not for pulmonary eosinophilia. In both STAT6‐ and STAT4‐deficient mice, the magnitude of inflammation remained unaltered. Our results suggest that RSV vaccine‐enhanced pulmonary injury and systemic disease are mediated by distinct pathways. This work was supported by the NIH (to SMV) and the American Heart Association (to EMC).