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.
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 Vbeta 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.
Haynes
Lia M
LM
Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Jones
Les P
LP
Barskey
Albert
A
Anderson
Larry J
LJ
Tripp
Ralph A
RA
D020816:Amino Acid Motifs; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics; D020523:Chemokines, CX3C / Q000378:metabolism*; D005260:Female; D005557:Formaldehyde; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D019707:Receptors, Chemokine / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013373:Substance P / Q000096:biosynthesis*; D014611:Vaccination / Q000009:adverse effects; D015164:Vaccines, Inactivated / Q000633:toxicity; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*; D014765:Viral Vaccines / Q000633:toxicity*
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D018925:Chemokines; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019707:Receptors, Chemokine; D015164:Vaccines, Inactivated; D014764:Viral Proteins; D014765:Viral Vaccines; D005557:Formaldehyde; D013373:Substance P