Comprehensive antigen screening identifies Moraxella catarrhalis proteins that induce protection in a mouse pulmonary clearance model

• Published in: PloS one Vol. 8; no. 5; p. e64422
• Main Authors: Smidt, Margarita, Bättig, Patrick, Verhaegh, Suzanne J C, Niebisch, Axel, Hanner, Markus, Selak, Sanja, Schüler, Wolfgang, Morfeldt, Eva, Hellberg, Christel, Nagy, Eszter, Lundberg, Urban, Hays, John P, Meinke, Andreas, Henriques-Normark, Birgitta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2013; Public Library of Science (PLoS)
• Subjects: Adhesins, Bacterial - genetics; Adhesins, Bacterial - immunology; Animals; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Apoptosis; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Vaccines - immunology; Biology; Blotting, Western; Cell surface; Child; Children; Chronic obstructive pulmonary disease; Consent; Cytochrome; Ear diseases; Enzyme-Linked Immunosorbent Assay; Ethics; Genomic libraries; Genomic Library; Heme; Hemeproteins - genetics; Hemeproteins - immunology; Host-Pathogen Interactions - immunology; Humans; In vivo methods and tests; Infectious diseases; Lung - immunology; Lung - microbiology; Medical screening; Medicin och hälsovetenskap; Medicine; Mice; Moraxella; Moraxella (Branhamella) catarrhalis - genetics; Moraxella (Branhamella) catarrhalis - immunology; Moraxella (Branhamella) catarrhalis - physiology; Moraxella catarrhalis; Moraxellaceae Infections - immunology; Moraxellaceae Infections - microbiology; Otitis media; Otitis Media - immunology; Otitis Media - microbiology; Pathogens; Peptides; Protein binding; Proteins; Streptococcus infections; Studies; Vaccines; Austria; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064422

Moraxella catarrhalis is one of the three most common causative bacterial pathogens of otitis media, however no effective vaccine against M. catarrhalis has been developed so far. To identify M. catarrhalis vaccine candidate antigens, we used carefully selected sera from children with otitis media and healthy individuals to screen small-fragment genomic libraries that are expressed to display frame-selected peptides on a bacterial cell surface. This ANTIGENome technology led to the identification of 214 antigens, 23 of which were selected by in vitro or in vivo studies for additional characterization. Eight of the 23 candidates were tested in a Moraxella mouse pulmonary clearance model, and 3 of these antigens induced significantly faster bacterial clearance compared to adjuvant or to the previously characterized antigen OmpCD. The most significant protection data were obtained with the antigen MCR_1416 (Msp22), which was further investigated for its biological function by in vitro studies suggesting that Msp22 is a heme binding protein. This study comprises one of the most exhaustive studies to identify potential vaccine candidate antigens against the bacterial pathogen M. catarrhalis.