title: Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages.
abstract: The mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4(+) T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration.
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA ; Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Ko
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA ; Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA ; National Institute of Biological Resources, Incheon, South Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
authors.forename: Ki-Hye
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA ; Department of Biology, Georgia State University, Atlanta, GA, USA.
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*
chemical_list: D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines
keywords: FI-RSV; RSV disease; VLP; alveolar macrophage; nanoparticle vaccine