title: Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45.
abstract: Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 10(5) could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany; Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pritsch
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany.
authors.forename: Najib
authors.initials: N
authors.lastname: Ben-Khaled
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, University of Munich (LMU), 80337 Munich, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Chaloupka
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, University of Munich (LMU), 80337 Munich, Germany; German Center for Lung Research, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Berens-Riha
authors.affiliation: Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany.
authors.forename: Annabell
authors.initials: A
authors.lastname: Peter
authors.affiliation: Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Liegl
authors.affiliation: Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Schubert
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Löscher
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), 80802 Munich, Germany; Department of Bacteriology, Max von Pettenkofer Institute (LMU), 81337 Munich, Germany; German Center for Infection Research (DZIF), Partner Site Munich, 80802 Munich, Germany; College of Public Health and Medical Science, Jimma University, Jimma, Ethiopia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wieser
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D002772:Cholera Toxin