title: Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge.
abstract: We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSV-specific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection.
authors.affiliation: Lung Immunology group, The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, UK.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Etchart
authors.forename: Bas
authors.initials: B
authors.lastname: Baaten
authors.forename: Svein Rune
authors.initials: SR
authors.lastname: Andersen
authors.forename: Lisa
authors.initials: L
authors.lastname: Hyland
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
authors.forename: Sam
authors.initials: S
authors.lastname: Hou
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D004802:Eosinophilia / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; D007071:Immunoglobulin A, Secretory; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D007371:Interferon-gamma; D002772:Cholera Toxin