A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specific for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for its functional activity in vitro and in a mouse model of colonization. Enzyme-linked immunosorbent assay (ELISA) demonstrated that the MAb 8E7 could be prepared to a high titer against LOS of the homologous strain 035E, and that it had bactericidal activity. MAb 8E7 reacted with M. catarrhalis serotype A and C LOSs but not serotype B LOS, as measured by ELISA and Western blotting. On the basis of published structures of LOSs, this suggests that the epitope recognized by MAb 8E7 is directed to a common sequence of either ␣-GlcNAc-(132)--Glc-(13 at the branch substituting position 4 of the trisubstituted Glc residue or a terminal tetrasaccharide ␣-Gal-(134)--Gal-(134)-␣-Glc-(132)--Glc-(13 at the branch substituting position 6 of the trisubstituted Glc residue. In a whole-cell ELISA, MAb 8E7 reacted with 70% of the 30 wild-type strains and clinical isolates tested. Immuno-electron microscopy demonstrated that MAb 8E7 reacted with a cell surface-exposed epitope of LOS on strain O35E. MAb 8E7 inhibited the adherence of strain O35E to Chang conjunctival epithelial cells by 90%. Passive immunization with MAb 8E7 could significantly enhance the clearance of strain O35E from mouse lungs in an aerosol challenge mouse model. This enhanced bacterial clearance was inhibited when MAb 8E7 was absorbed by M. catarrhalis serotype A LOS, indicating that the M. catarrhalis LOS-directed antibody may play a major role in the enhancement of M. catarrhalis clearance from lungs. These data suggest that MAb 8E7, which recognizes surface-exposed LOS of M. catarrhalis, is a protective antibody against M. catarrhalis.Moraxella catarrhalis is an important and common cause of otitis media in children as well as bronchopulmonary infection in the elderly, especially those with underlying pulmonary disease or a compromised immune system (4, 5, 26). Sporadic cases of conjunctivitis, meningitis, endocarditis, ophthalmia neonatorum, keratitis, urethritis, peritonitis, and septicemia have also been reported to be due to M. catarrhalis (25). In addition, an extremely high carriage rate (56%) has been reported for healthy children (11,12,18). Although the pathogenesis of M. catarrhalis infection is not fully understood, it is generally agreed that it has several virulence factors involved in colonization and adherence that enable it to evade the normal host defense mechanisms and that allow it to cause disease.The lipooligosaccharide (LOS) from M. catarrhalis is a major component of the outer membrane and is a potential virulence factor (7, 13). LOS consists of an oligosaccharide and lipid A and is similar to the lipopolysaccharide (LPS) of gramnegative enteric pathogens, but it lacks the O-antigenic side chain of repeating units characteristic of classical LPS. LOS has been demonstrated to be an important virulence factor for such gram-negative bacteria as Neisseria meningitidis, Neisseria gonorrhoeae...