Biological and Immunological Characteristics of Lipooligosaccharide-Based Conjugate Vaccines for Serotype C Moraxella catarrhalis

摘要

Moraxella catarrhalis is an important bacterial cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS), a major surface antigen of this bacterium, is a potential vaccine component against the organism. There are three major LOS serotypes (serotypes A, B, and C) in clinical isolates of M. catarrhalis. Our previous studies demonstrated that serotype A and B LOS-based conjugates were immunogenic in animals and elicited bactericidal antibodies. In this study, LOS from serotype C strain 26404 was isolated, detoxified, and conjugated to tetanus toxoid (TT) or the cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT, dLOS-CRM-1, and dLOS-CRM-2 vaccine candidates. The molar ratios (dLOS/protein) of the resulting conjugates were 47:1, 19:1, and 32:1, respectively, while the weight ratios were 0.94, 0.84 and 1.44, respectively. All conjugates were highly immunogenic in both mouse and rabbit models. Three subcutaneous injections of each conjugate formulated with the Ribi adjuvant elicited >700-fold increases in serum anti-LOS immunoglobulin G levels in mice (5 μg of dLOS) and >2,000-fold increases in rabbits (50 μg of dLOS). The resulting mouse and rabbit antisera showed complement-mediated bactericidal activity against the homologous strain. In addition, a representative rabbit antiserum showed bactericidal activity against 14 of 18 testable strains, and this bactericidal activity could be 100% inhibited by the serotype C or A LOS but only 30% inhibited by the serotype B LOS. These results indicate that the serotype C LOS-based conjugates can be used as vaccine components for further investigation in humans.