title: Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis.
abstract: Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test. The detoxified LOS (dLOS) was coupled to tetanus toxoid (TT) or high-molecular-weight proteins (HMP) from nontypeable Haemophilus influenzae through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratios of dLOS to TT and HMP conjugates were 19:1 and 31:1, respectively. The antigenicity of the two conjugates was similar to that of the LOS, as determined by double immunodiffusion. Subcutaneous or intramuscular injection of both conjugates elicited a 50- to 100-fold rise in the geometric mean of immunoglobulin G (IgG) to the homologous LOS in mice after three injections and a 350- to 700-fold rise of anti-LOS IgG in rabbits after two injections. The immunogenicity of the conjugate was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced antisera had complement-mediated bactericidal activity against the homologous strain and heterologous strains of M. catarrhalis. These results indicate that a detoxified LOS-protein conjugate is a candidate for immunization against M. catarrhalis diseases.
authors.affiliation: Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA. xgu@pop.nidcd.nih.gov
authors.forename: X X
authors.initials: XX
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: S J
authors.initials: SJ
authors.lastname: Barenkamp
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
authors.forename: C M
authors.initials: CM
authors.lastname: Tsai
authors.forename: D J
authors.initials: DJ
authors.lastname: Lim
authors.forename: J
authors.initials: J
authors.lastname: Battey
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D007106:Immune Sera / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D001936:Moraxella catarrhalis / Q000276:immunology*; D011817:Rabbits; D013745:Tetanus Toxoid / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007106:Immune Sera; D008070:Lipopolysaccharides; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C023023:lipid-linked oligosaccharides