Mining the Moraxella catarrhalis genome: identification of potential vaccine antigens expressed during human infection.

Moraxella catarrhalis is an important cause of respiratory infections in adults and otitis media in children. Developing an effective vaccine would reduce the morbidity, mortality, and costs associated with such infections. An unfinished genome sequence of a strain of M. catarrhalis available in the GenBank database was analyzed, and open reading frames predicted to encode potential vaccine candidates were identified. Three genes encoding proteins having molecular masses of approximately 22, 75, and 78 kDa (designated Msp [Moraxella surface proteins]) (msp22, msp75, and msp78, respectively) were determined to be conserved by competitive hybridization using a microarray, PCR, and sequencing of the genes in clinical isolates of M. catarrhalis. The genes were transcribed when M. catarrhalis was grown in vitro. These genes were amplified by PCR and cloned into Escherichia coli expression vectors. Recombinant proteins were generated and then studied using enzyme-linked immunosorbent assays with preacquisition and postclearance serum and sputum samples from 31 adults with chronic obstructive pulmonary disease (COPD) who acquired and cleared M. catarrhalis. New antibody responses to the three proteins were observed for a small proportion of the patients with COPD, indicating that these proteins were expressed during human infection. These studies indicate that the Msp22, Msp75, and Msp78 proteins, whose genes were discovered using genome mining, are highly conserved among strains, are expressed during human infection with M. catarrhalis, and represent potential vaccine antigens.

Characterization of proteins Msp22 and Msp75 as vaccine antigens of Moraxella catarrhalis.

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.