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Journal of Virology, September 2003, p. 9831-9844, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.9831-9844.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Enhanced Disease and Pulmonary Eosinophilia Associated with Formalin-Inactivated Respiratory Syncytial Virus Vaccination Are Linked to G Glycoprotein CX3C-CX3CR1 Interaction and Expression of Substance P

Lia M. Haynes, Les P. Jones, Albert Barskey, Larry J. Anderson, and Ralph A. Tripp*

Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333

Received 12 March 2003/ Accepted 17 June 2003

Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine or RSV G glycoprotein results in enhanced pulmonary disease after live RSV infection. Enhanced pulmonary disease is characterized by pulmonary eosinophilia and is associated with a substantial inflammatory response. We show that the absence of the G glycoprotein or G glycoprotein CX3C motif during FI-RSV vaccination or RSV challenge of FI-RSV-vaccinated mice, or treatment with anti-substance P or anti-CX3CR1 antibodies, reduces or eliminates enhanced pulmonary disease, modifies T-cell receptor Vß usage, and alters CC and CXC chemokine expression. These data suggest that the G glycoprotein, and in particular the G glycoprotein CX3C motif, is key in the enhanced inflammatory response to FI-RSV vaccination, possibly through the induction of substance P.

* Corresponding author. Mailing address: Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333. Phone: (404) 639-0753. Fax: (404) 639-4005. E-mail: rgt3{at}cdc.gov.

Journal of Virology, September 2003, p. 9831-9844, Vol. 77, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.18.9831-9844.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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