title: Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice.
abstract: Protective mechanisms underlying the responses to mucosal vaccination are not yet clearly defined. Using the natural mouse pneumovirus pathogen, pneumonia virus of mice (PVM), we explore responses of wild type and interferon-gamma (IFNgamma) receptor gene-deleted mice to virulent challenge after mucosal vaccination with an attenuated virus strain. Serum neutralizing antibodies develop after intranasal inoculation with 30 pfu of attenuated, replication-competent PVM strain 15, which correlate with diminished gross and microscopic pulmonary pathology and protection from weight loss in response to subsequent challenge with the virulent parent PVM strain J3666. Virus replication in response to challenge was blunted in PVM strain 15 vaccinated mice, as was local production of secretory mediators IFNgamma, TNF-alpha, MIP-1 alpha, and MIP-2. Interestingly, responses of vaccinated IFNgamma receptor gene-deleted mice were indistinguishable from those of the wild type, suggesting that IFNgamma signaling may not be crucial for the generation of adaptive responses to pneumovirus infection in vivo.
authors.affiliation: Western Veterinary Medical College, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: John A
authors.initials: JA
authors.lastname: Ellis
authors.forename: Brittany V
authors.initials: BV
authors.lastname: Martin
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waldner
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Dyer
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018111:Pneumovirus / Q000276:immunology*; D018186:Pneumovirus Infections / Q000276:immunology / Q000517:prevention & control*; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*; D000096743:Interferon gamma Receptor
chemical_list: D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D014765:Viral Vaccines; D000096743:Interferon gamma Receptor; C404915:Cxcl2 protein, mouse