title: Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection.
abstract: As respiratory syncytial virus (RSV) targets the mucosal surfaces of the respiratory tract, induction of both systemic and mucosal immunity will be critical for optimal protection. In this study, the ability of an intranasally delivered, formalin-inactivated bovine RSV (FI-BRSV) vaccine co-formulated with CpG oligodeoxynucleotides (ODN) and polyphosphazenes (PP) to induce systemic and mucosal immunity, as well as protection from BRSV challenge, was evaluated. Intranasal immunization of mice with FI-BRSV formulated with CpG ODN and PP resulted in both humoral and cell-mediated immunity, characterized by enhanced production of BRSV-specific serum IgG, as well as increased gamma interferon and decreased interleukin-5 production by in vitro-restimulated splenocytes. These mice also developed mucosal immune responses, as was evident from increased production of BRSV-specific IgG and IgA in lung-fragment cultures. Indeed, the increases in serum and mucosal IgG, and in particular mucosal IgA and virus-neutralizing antibodies, were the most critical differences observed between FI-BRSV formulated with both CpG ODN and PP in comparison to formulations with CpG ODN, non-CpG ODN or PP individually. Finally, FI-BRSV/CpG/PP was the only formulation that resulted in a significant reduction in viral replication upon BRSV challenge. Co-formulation of CpG ODN and PP is a promising new vaccine platform technology that may have applications in mucosal immunization in humans.
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: John W
authors: JW
authors: Mapletoft
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: Mustapha
authors: M
authors: Oumouna
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: Jennifer
authors: J
authors: Kovacs-Nolan
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: Laura
authors: L
authors: Latimer
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: George
authors: G
authors: Mutwiri
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: Lorne A
authors: LA
authors: Babiuk
authors: Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
authors: Sylvia
authors: S
authors: van Drunen Littel-van den Hurk
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D015226:Dinucleoside Phosphates; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000627:therapeutic use*; D009943:Organophosphorus Compounds; D011108:Polymers; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D012192:Retroviridae Infections / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016092:Spumavirus / Q000276:immunology*; D015164:Vaccines, Inactivated
chemical_list: D015226:Dinucleoside Phosphates; D007371:Interferon-gamma; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D011108:Polymers; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; C108974:poly(phosphazene); C015772:CpG dinucleotide