Enhancement of clearance of bacteria from murine lungs by immunization with detoxified lipooligosaccharide from Moraxella catarrhalis conjugated to proteins

Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-pr otein conjugates induced a significant rise of bactericidal anti-LOS antibo dies in animals. This study reports the effect of active or passive immuniz ation with the conjugates or their antiserum on pulmonary clearance of M. c atarrhalis in an aerosol challenge mouse model. Mice were injected subcutan eously with dLOS-tetanus toxoid (dLOS-TT), dLOS-high-molecular-weight prote ins (dLOS-HMP) from nontypeable Haemophilus influenzae (NTHi), or nonconjug ated materials in Ribi adjuvant and then challenged with M. catarrhalis str ain 2-5238 or O35E or NTHi strain 12. Immunization with dLOS-TT or dLOS-HMP generated a significant rise of serum anti-LOS immunoglobulin G and 68% an d 35 to 41% reductions of bacteria in lungs compared with the control (P < 0.01) following challenge with homologous strain 25238 and heterologous str ain O35E, respectively. Serum anti-LOS antibody levels correlated with its bactericidal titers against M. catarrhalis and bacterial CFU in lungs. Addi tionally, immunization with dLOS-HMP generated a 54% reduction of NTHi stra in 12 compared with the control (P < 0.01). Passive immunization with a rab bit antiserum against dLOS-TT conferred a significant reduction of strain 2 5238 CFU in lungs in a dose- and time-dependent pattern compared with preim mune serum-treated mice. Kinetic examination of lung tissue sections demons trated that antiserum-treated mice initiated and offset inflammatory respon ses more rapidly than preimmune serum-treated mice. These data indicate tha t LOS antibodies (whether active or passive) play a major role in the enhan cement of pulmonary clearance of different test strains of M. catarrhalis i n mice. In addition, dLOS-HMP is a potential candidate for a bivalent vacci ne against M. catarrhalis and NTHi infections.