Abstract

A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease Timothy F. Murphy a , b , c , Aimee L. Brauer a , b , Antoinette Johnson a , b , Gregory E. Wilding d , Mary Koszelak-Rosenblum e , f and Michael G. Malkowski e , f a Division of Infectious Diseases, Department of Medicine, University at Buffalo, the State University of New York, Buffalo, New York, USA b Clinical and Translational Research Center, University at Buffalo, the State University of New York, Buffalo, New York, USA c Department of Microbiology and Immunology, University at Buffalo, the State University of New York, Buffalo, New York, USA d Department of Biostatistics, University at Buffalo, the State University of New York, Buffalo, New York, USA e Department of Structural Biology, University at Buffalo, the State University of New York, Buffalo, New York, USA f Hauptman Woodward Medical Research Institute, Buffalo, New York, USA Marcela F. Pasetti , Editor University of Maryland School of Medicine ABSTRACT Moraxella catarrhalis is an exclusively human respiratory tract pathogen that is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent these infections would have a major impact on reducing the substantial global morbidity and mortality in these populations. Through a genome mining approach, we identified AfeA, an ∼32-kDa substrate binding protein of an ABC transport system, as an excellent candidate vaccine antigen. Recombinant AfeA was expressed and purified and binds ferric, ferrous, manganese, and zinc ions, as demonstrated by thermal shift assays. It is a highly conserved protein that is present in all strains of M. catarrhalis . Immunization with recombinant purified AfeA induces high-titer antibodies that recognize the native M. catarrhalis protein. AfeA expresses abundant epitopes on the bacterial surface and induces protective responses in the mouse pulmonary clearance model following aerosol challenge with M. catarrhalis . Finally, AfeA is expressed during human respiratory tract infection of adults with chronic obstructive pulmonary disease (COPD). Based on these observations, AfeA is an excellent vaccine antigen to be included in a vaccine to prevent infections caused by M. catarrhalis . KEYWORDS ABC transporters Moraxella catarrhalis immunization otitis media pulmonary infection surface antigens vaccines