title: Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon.
abstract: In order to investigate if immune responses to the fusion (F) protein of respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant vaccinia viruses (rVV) carrying both the F gene of RSV and the gene for murine interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-gamma) were constructed. In vitro characterization of rVV revealed that insertion of the cytokine gene into the VP37 locus of the vaccinia virus genome resulted in 100- to 1,000-fold higher expression than insertion of the same gene into the thymidine kinase (TK) locus. In comparison, only a two- to fivefold difference in the level of expression of the F protein was observed when the gene was inserted into either of these two loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-gamma cleared rVV more rapidly than mice inoculated with a control rVV and developed only low levels of RSV-specific serum antibody. In addition, these recombinants were much less effective at priming RSV-specific memory cytotoxic T lymphocytes (CTL) and IFN-gamma production by spleen cells than rVV expressing the F protein alone. In contrast, mice vaccinated with rVV expressing high levels of IL-4 showed signs of delayed rVV clearance. RSV-specific serum antibody responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as there was a significant reduction in IgG2a antibody responses compared with serum antibody responses in mice vaccinated with rVV expressing the F protein alone. However, vaccination with rVV expressing the F protein together with high levels of IL-4 did not alter the development of RSV-specific memory CTL or IFN-gamma production by RSV-restimulated splenocytes.
authors.affiliation: BBSRC, Institute for Animal Health, Newbury, Berkshire, 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: Cook
authors.forename: J A
authors.initials: JA
authors.lastname: Melero
authors.forename: G
authors.initials: G
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D015707:HN Protein; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014774:Virulence; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015707:HN Protein; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D015847:Interleukin-4; D007371:Interferon-gamma