Functional characteristics of a protective monoclonal antibody against serotype A and C lipooligosaccharides from Moraxella catarrhalis

A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specif ic for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for it s 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 tha t it had bactericidal activity, MAb 8E7 reacted with M. catarrhalis serotyp e A and C LOSs but not serotype B LOS, as measured by ELISA and Western blo tting. 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 a lpha -GlcNAc-(1-->2)-beta -Glc-(1--> at the branch substituting position 4 of the trisubstituted Glc residue or a terminal tetrasaccharide alpha -Gal- (1-->4)-beta -Gal-(1-->4)-alpha -Glc-(1-->2)-beta -Glc-(1--> 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 is olates tested. Immune-electron microscopy demonstrated that MAb 8E7 reacted with a cell surface-exposed epitope of LOS on strain O35E, MAb 8E7 inhibit ed the adherence of strain 035E to Chang conjunctival epithelial cells by 9 0%. Passive immunization with MAb 8E7 could significantly enhance the clear ance of strain O35E from mouse lungs in an aerosol challenge mouse model. T his enhanced bacterial clearance was inhibited when MAb 8E7 was absorbed by ill. catarrhalis serotype A LOS, indicating that the M, catarrhalis LOS-di rected antibody may play a major role in the enhancement of M. catarrhalis clearance from lungs. These data suggest that MAb 8E7, which recognizes sur face-exposed LOS of M. catarrhalis, is a protective antibody against M, cat arrhalis.