title: Priming with a secreted form of the fusion protein of respiratory syncytial virus (RSV) promotes interleukin-4 (IL-4) and IL-5 production but not pulmonary eosinophilia following RSV challenge.
abstract: The attachment (G) protein of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. BALB/c mice scarified with vaccinia virus (VV) expressing the secreted form develop a greater pulmonary eosinophilic influx following RSV challenge than do mice scarified with VV expressing the membrane-anchored form. To determine if a soluble form of an RSV protein was sufficient to induce eosinophilia following RSV challenge, a cDNA that encoded a secreted form of the fusion (F) protein of RSV was constructed and expressed in VV (VV-Ftm(-)). Splenocytes and lung lymphocytes from mice primed with VV-Ftm(-) produced significantly more of the Th2 cytokines interleukin-4 (IL-4) and IL-5 than did mice vaccinated with VV expressing either the native (membrane-anchored) form of the F protein or the G protein. Although mice scarified with VV-Ftm(-) developed a slight increase in the number of pulmonary eosinophils following RSV infection, the increase was not as great as that seen in VV-G-primed mice. Despite the increased IL-4 and IL-5 production and in contrast to mice primed with VV-G, mice primed with VV-Ftm(-) developed RSV-specific cytotoxic T lymphocytes (CTL) and maintained high levels of gamma interferon production. These data demonstrate that recombinant VV strains expressing soluble forms of RSV proteins induce immune responses that are more Th2-like. However, this change alone does not appear sufficient to induce vaccine-augmented disease in the face of active CD8(+) CTL populations.
authors.affiliation: Institute for Animal Health, Compton, Newbury RG20 7NN, United Kingdom. Gary.Bembridge@bbsrc.ac.uk
authors.forename: G P
authors.initials: GP
authors.lastname: Bembridge
authors.forename: J A
authors.initials: JA
authors.lastname: Lopez
authors.forename: R
authors.initials: R
authors.lastname: Bustos
authors.forename: J A
authors.initials: JA
authors.lastname: Melero
authors.forename: R
authors.initials: R
authors.lastname: Cook
authors.forename: H
authors.initials: H
authors.lastname: Mason
authors.forename: G
authors.initials: G
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015707:HN Protein; D006801:Humans; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D007700:Kinetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D015707:HN Protein; D015848:Interleukin-5; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D015847:Interleukin-4; D001616:beta-Galactosidase