title: Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung.
abstract: Cytomegalovirus vectors are promising delivery vehicles for vaccine strategies that aim to elicit effector CD8+ T cells. To determine how the route of immunization affects CD8+ T-cell responses in the lungs of mice vaccinated with a murine cytomegalovirus vector expressing the respiratory syncytial virus matrix (M) protein, we infected CB6F1 mice via the intranasal or intraperitoneal route and evaluated the M-specific CD8+ T-cell response at early and late time points. We found that intranasal vaccination generated robust and durable tissue-resident effector and effector memory CD8+ T-cell populations that were undetectable after intraperitoneal vaccination. The generation of these antigen-experienced cells by intranasal vaccination resulted in earlier T-cell responses, interferon gamma secretion, and viral clearance after respiratory syncytial virus challenge. Collectively, these findings validate a novel approach to vaccination that emphasizes the route of delivery as a key determinant of immune priming at the site of vulnerability.
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.|Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, District of Columbia, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Morabito
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Ruckwardt
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Redwood
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Moin
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.|Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D007156:Immunologic Memory; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014611:Vaccination; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D014763:Viral Matrix Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma