Moraxella catarrhalis is a respiratory tract pathogen causing otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. This study examined two newly identified proteins as potential vaccine antigens. Antisera raised to recombinant purified proteins Msp22 and Msp75 recognized corresponding native proteins in multiple strains of M. catarrhalis. Vaccine formulations individually administered subcutaneously and intranasally showed enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model by both routes of administration. Msp22 and Msp75 are antigenically conserved proteins that induce potentially protective immune responses and should be examined further as vaccine antigens for M. catarrhalis.