title: Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation.
abstract: The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8(+) T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8(+) central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.
authors.affiliation: VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Garg
authors.affiliation: VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Latimer
authors.affiliation: Veterinary Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Simko
authors.affiliation: Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.|VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gerdts
authors.affiliation: Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.|VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Potter
authors.affiliation: Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.|VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
authors.forename: S
authors.initials: S
authors.lastname: van Drunen Littel-van den Hurk
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000032:analysis; D000914:Antibodies, Viral / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D011070:Poly I-C / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009943:Organophosphorus Compounds; D011108:Polymers; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014760:Viral Fusion Proteins; C108974:poly(phosphazene); D011070:Poly I-C