title: Exploration of Moraxella catarrhalis outer membrane proteins, CD and UspA, as new carriers for lipooligosaccharide-based conjugates.
abstract: Moraxella catarrhalis outer membrane proteins, CD and ubiquitous surface protein A (UspA), were used as carriers for M. catarrhalis detoxified lipooligosaccharide (dLOS)-based conjugates. Our study was designed to investigate the feasibility of CD and UspA as protein carriers for dLOS-based conjugates and their possible synergic effects on protection from both anti-LOS and anti-CD or anti-UspA antibody responses. Female Balb/c mice were immunized subcutaneously three times with dLOS-CD or dLOS-UspA conjugate in Ribi adjuvant. Antisera elicited by the conjugates showed high titers of specific anti-LOS antibodies with complement-dependent bactericidal activity towards M. catarrhalis strain 25238. In a mouse aerosol challenge model, mice immunized with both conjugates showed a significant enhancement of the clearance of strain 25238 from lungs as compared with the control mice. Although both conjugates elicited reduced (relative to unconjugated CD or UspA) but significant levels of anti-CD or UspA antibodies, they did not show synergetic effects with anti-LOS antibodies on the bactericidal activity or the pulmonary bacterial clearance. Nevertheless, CD and UspA are safe and effective new carriers for dLOS-based or other potential carbohydrate-based conjugate vaccines to help thymus-independent carbohydrate antigens for production of anti-carbohydrate antibodies against target pathogens.
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Hu
authors.forename: Julie
authors.initials: J
authors.lastname: Berry
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Gu
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D007114:Immunization; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D005779:Immunodiffusion; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D001936:Moraxella catarrhalis / Q000737:chemistry* / Q000276:immunology; D045828:Moraxellaceae Infections / Q000276:immunology* / Q000517:prevention & control; D011897:Random Allocation; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D018796:Immunoconjugates; D008070:Lipopolysaccharides; C089675:UspA protein, Moraxella catarrhalis; D018074:Vaccines, Conjugate; C023023:lipid-linked oligosaccharides