title: Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.
abstract: Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. Electronic address: H.Maunder@oxfordbiomedica.co.uk.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Maunder
authors.affiliation: The Pirbright Institute, Pirbright, Woking GU24 0NF, UK. Electronic address: geraldine.taylor@pirbright.ac.uk.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Taylor
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. Electronic address: keith.leppard@warwick.ac.uk.
authors.forename: Keith N
authors.initials: KN
authors.lastname: Leppard
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK. Electronic address: a.j.easton@warwick.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Easton
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D008297:Male; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus / Q000235:genetics / Q000276:immunology*; D011024:Pneumonia, Viral / Q000517:prevention & control / Q000662:veterinary*; D018186:Pneumovirus Infections / Q000517:prevention & control*; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines
keywords: Adenovirus vector; HRSV; Intranasal immunisation; PVM; Vaccine