title: Sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against RSV in cotton rats.
abstract: The respiratory syncytial virus (RSV) is responsible for as many as 199000 annual deaths worldwide. Currently, there is no standard treatment for RSV disease and no vaccine. Sendai virus (SeV) is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific B cell and T cell activities in systemic and mucosal tissues. The virus serves as a gene delivery system as well as a Jennerian vaccine against its close cousin, human parainfluenza virus type 1. Here we describe the testing of a recombinant SeV (SeVRSV-Fs) that expresses an unconstrained, secreted RSV-F protein as a vaccine against RSV in cotton rats. After a single intranasal immunization of cotton rats with SeVRSV-Fs, RSV-specific binding and neutralizing antibodies were generated. These antibodies exhibited cross-reactivity with both RSV A and B isolates. RSV-F-specific IFN-γ-producing T cells were also activated. The SeVRSV-Fs vaccine conferred protection against RSV challenge without enhanced immunopathology. In total, results showed that an SeV recombinant that expresses RSV F in an unconstrained, soluble form can induce humoral and cellular immunity that protects against infection with RSV.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Present Address: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Present Address: Department of Technical Development, Novartis Vaccines, Cambridge, MA 02139, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Slobod
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Bart G
authors.initials: BG
authors.lastname: Jones
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sealy
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Present Address: Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Takimoto
authors.affiliation: Animal Resource Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Present Address: Division of Animal Care, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Surman
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Russell
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Allen
authors.initials: A
authors.lastname: Portner
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA julia.hurwitz@stjude.org.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000378:metabolism*; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014760:Viral Fusion Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: Sendai virus; protection; respiratory syncytial virus; secreted fusion protein; unconstrained F; vaccine