Identification and characterization of outer membrane proteins G1a and G1b of Moraxella catarrhalis

Moraxella catarrhalis is an important cause of otitis media and lower respiratory tract infections in patients with chronic obstructive pulmonary disease (COPD). Due to the morbidity and mortality of the diseases caused by M. catarrhalis there is an interest in developing a vaccine. Vaccine development has focused on outer membrane proteins (OMP) like OMP G1. Isoelectric focusing of outer membrane preparations and amino-terminal protein sequence of the OMP G1 band revealed that the band is actually two proteins. These two proteins have been designated OMP G1a and OMP G1b. OMP G1a is a lipoprotein with an isoelectric point of 4. OMP G1b contains an unblocked amino-terminus and has an isoelectric point of 9. The genes that encode OMP G1a and OMP G1b were sequenced from 25 clinically and geographically diverse strains and demonstrated that they are highly conserved among strains of M. catarrhalis. The human systemic and mucosal immune responses to purified recombinant OMP G1a and OMP G1b were determined by using human serum and sputum samples that were collected as part of a prospective study of COPD in ELISA. The ELISAs utilized serum and sputum supernatant pairs associated with M. catarrhalis acquisition and clearance from the respiratory tract of adults with COPD. Overall, 23% of adults with COPD developed either a serum IgG response or a sputum supernatant IgA response to OMP G1a, while 39% made either a serum IgG response or a sputum supernatant IgA response to OMP G1b following acquisition and clearance of M. catarrhalis. These observations demonstrate that OMP G1a and OMP G1b were expressed during infections of the human respiratory tract and are targets of the systemic and mucosal immune responses. Adsorption assays were carried out with the serum samples that contained new IgG responses to OMP G1a and OMP G1b. The serum IgG response to OMP G1b was directed to surface epitopes, while the serum IgG response to OMP G1a was directed to non-surface exposed epitopes. These observations provide a strong rationale to perform additional research in evaluating OMP G1a and OMP G1b as potential vaccine antigens for M. catarrhalis.