title: The effect of vaccines based on ovalbumin coupled to gas-filled microbubbles for reducing infection by ovalbumin-expressing Listeria monocytogenes.
abstract: Gas-filled microbubbles (MB) are a very promising alternative to the currently evaluated lipid- or polymer-based particulate Ag delivery systems. We recently demonstrated the ability of MB to deliver associated Ag to DC, to activate them and thereby induce both humoral and cellular immune responses. We now extended the characterization of MB as antigen-delivery system by appraising the efficiency of MB-associated ovalbumin (OVA-MB) at protecting mice against pathogen infection. Ultrasound-mediated imaging demonstrated that the administration of OVA via MB generates a depot at the injection site that lasts for several hours. We found that OVA-MB injected subcutaneously is far more effective at inducing specific Ab and T cell immunity than immunization with free OVA. Moreover, a covalent link between MB and OVA causes a stronger bias towards a Th1-type of immune response than adsorption of the Ag or its covalent link to liposomes of the same lipid composition. Finally, vaccination of mice with OVA-MB partially protects against a systemic infection with OVA-expressing Listeria monocytogenes. The vaccine induces specific effector CD8 T cell responses capable of decreasing more than 100 fold the bacterial load. MB thus represent a potent Ag delivery system for vaccination against intracellular infectious agents.
authors.affiliation: R&D Laboratory, Division of Immunology and Allergy, University State Hospital (CHUV), Lausanne, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bioley
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Anne
authors.initials: A
authors.lastname: Lassus
authors.forename: Jacques
authors.initials: J
authors.lastname: Terrettaz
authors.forename: François
authors.initials: F
authors.lastname: Tranquart
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D005740:Gases / Q000737:chemistry*; D056724:Immunity, Humoral / Q000276:immunology; D007267:Injections; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D010047:Ovalbumin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014465:Ultrasonics; D014611:Vaccination
chemical_list: D001428:Bacterial Vaccines; D005740:Gases; D010047:Ovalbumin