title: Vaccination with the RSV fusion protein formulated with a combination adjuvant induces long-lasting protective immunity.
abstract: Respiratory syncytial virus (RSV) is one of the primary causative agents of upper and lower respiratory tract infections in young children, in particular infants. Recently, we reported the protective efficacy of a RSV vaccine formulation consisting of a truncated version of the fusion (F) protein formulated with a Toll-like receptor (TLR) agonist and an immunostimulatory peptide in a carrier system (ΔF/TriAdj). To evaluate the duration of immunity induced by this vaccine candidate, we carried out long-term trials. The ΔF was formulated with triple adjuvant (TriAdj) containing either polyinosinic : polycytidylic acid (polyI : C) or cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) and administered intranasally to mice. One year after the second vaccination all mice were challenged with RSV. Both ΔF/TriAdj formulations mediated the induction of high levels of IgG1, IgG2a and virus-neutralizing antibodies, and IgA in the lungs. Based on the numbers of IFN-γ- and IL-5-secreting cells in the spleen, the immune response was slightly T-helper cell type 1 (Th1)-biased. This was confirmed by the presence of F85-93-specific CD8(+) effector T cells in the lungs of both ΔF/TriAdj(polyI : C)- and ΔF/TriAdj(CpG)-immunized mice. Both ΔF/TriAdj formulations induced RSV-specific CD8(+) T cells. However, ΔF/TriAdj(polyI : C) generated significantly higher IgG affinity maturation and higher numbers of RSV-specific CD8(+) effector memory T cells in lungs and CD8(+) central memory T cells in spleen and lymph nodes than ΔF/TriAdj(CpG). After RSV challenge, no virus replication and no evidence of vaccine-induced pathology were detected in mice immunized with either of the ΔF/TriAdj formulations, demonstrating that the duration of immunity induced with these vaccines is at least one year.
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: VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.|Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Gerdts
authors.affiliation: VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.|Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Potter
authors.affiliation: VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.|Microbiology & Immunology, 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*; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D016207:Cytokines / Q000276:immunology; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D011070:Poly I-C / Q000008:administration & dosage; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D016207:Cytokines; C526850:F protein, human respiratory syncytial virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D011070:Poly I-C