EVALUATION OF PURIFIED USPA FROM MORAXELLA-CATARRHALIS AS A VACCINE IN A MURINE MODEL AFTER ACTIVE IMMUNIZATION

Moraxella catarrhalis causes otitis media, laryngitis, and respiratory infections in humans. A high-molecular-weight outer membrane protein from this bacterium named ubiquitous surface protein A (UspA) is prese nt on all isolates. A monoclonal antibody (MAb) to UspA that recognize s a conserved epitope of this protein has been shown to promote pulmon ary clearance of bacteria in passively immunized mice. In the present study, nl. catarrhalis heterologous isolates were screened by dot blot with a panel of four additional MAbs specific for surface-exposed epi topes of UspA from M. catarrhalis isolate O35E. Three of the MAbs were specific for O35E, and the fourth reacted with 17 (74%) of the 23 iso lates tested. Thus, UspA contains highly conserved, semiconserved, and variable surface-exposed epitopes. The UspA was purified from the O35 E isolate by ion-exchange and size-exclusion chromatography, formulate d with the adjuvant QS-21, and used to immunize BALB/c mice. Upon pulm onary challenge with either O35E or the heterologous isolate TTA24, si gnificantly fewer bacteria were recovered from the lungs of immunized mice 6 h postchallenge than from control mice. The immune sera from mi ce or guinea pigs contained high titers of antibodies to the homologou s isolate and heterologous isolates in a whole-bacterial-cell enzyme-l inked immunosorbent assay. Sera against UspA, whether prepared in mice or guinea pigs, had complement-dependent bactericidal activity toward homologous and 11 heterologous M. catarrhalis isolates. These results indicate that the conserved epitopes of the UspA are highly immunogen ic and elicit broadly reactive and biologically functional antibodies. UspA may offer protection against M. catarrhalis infections and is be ing further evaluated as a vaccine candidate.