Synthesis and characterization of lipooligosaccharide-based conjugates as vaccine candidates for Moraxella (Branhamella) catarrhalis

• Published in: Infection and immunity 1998-05, Vol.66 (5), p.1891-1897
• Main Authors: GU, X.-X, JING CHEN, BARENKAMP, S. J, ROBBINS, J. B, TSAI, C.-M, LIM, D. J, BATTEY, J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Bacterial - blood; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Immune Sera - immunology; Lipopolysaccharides - immunology; Mice; Microbial Immunity and Vaccines; Microbiology; Moraxella (Branhamella) catarrhalis - immunology; Rabbits; Tetanus Toxoid - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Conjugate - immunology; Vaccines, Synthetic - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.66.5.1891-1897.1998

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.