title: Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein.
abstract: Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcγRI and FcγRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection.
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium bert.schepens@irc.vib-ugent.be xavier.saelens@irc.vib-ugent.be.
authors.forename: Bert
authors.initials: B
authors.lastname: Schepens
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Sedeyn
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vande Ginste
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: De Baets
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Michael
authors.initials: M
authors.lastname: Schotsaert
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Kenny
authors.initials: K
authors.lastname: Roose
authors.affiliation: Laboratory of Clinical Virology, Rega Institute for Medical Research KU Leuven, Leuven, Belgium.
authors.forename: Lieselot
authors.initials: L
authors.lastname: Houspie
authors.affiliation: Laboratory of Clinical Virology, Rega Institute for Medical Research KU Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gilbert
authors.affiliation: Department of Molecular Cell Biology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Piedra
authors.affiliation: VIB Inflammation Research Center, Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium bert.schepens@irc.vib-ugent.be xavier.saelens@irc.vib-ugent.be.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D047589:Leukocyte Reduction Procedures; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D016205:Sigmodontinae
chemical_list: D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines; D015682:Retroviridae Proteins, Oncogenic; C056150:small hydrophobic protein, virus
keywords: Fcγ receptor; alveolar macrophages; human respiratory syncytial virus; small hydrophobic protein; vaccine