Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease.
Respiratory syncytial virus (RSV) infection of BALB/c mice previously immunized with a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV (vacvG) results in pulmonary eosinophilia, which mimics the response of formalin-inactivated RSV-vaccinated children, as well as increased weight loss, clinical illness, and enhanced pause (Penh). We show that RSV infection of eosinophil-deficient mice previously immunized with vacvG results in the development of increased weight loss, clinical illness, and Penh similar to that in wild-type controls. These measures of RSV vaccine-enhanced disease are dependent upon STAT4. Interestingly, neither IL-12 nor IL-23, the two most common STAT4-activating cytokines, proved necessary for the development of disease. We demonstrate that IFN-gamma, which is produced following STAT4 activation, contributes to clinical illness and increased Penh, but not weight loss. Our results have important implications for future RSV vaccine design, suggesting that enhancing a Th1 response may exacerbate disease.
Castilow
Elaine M
EM
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
Legge
Kevin L
KL
Varga
Steven M
SM
D000818:Animals; D004804:Eosinophils / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000276:immunology / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D053759:Interleukin-23; D022261:Respiratory Syncytial Virus Vaccines; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D018664:Interleukin-12; D007371:Interferon-gamma