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Human antibody response to outer membrane protein G1a, a lipoprotein of Moraxella catarrhalis
Diana G Adlowitz1, Sanjay Sethi, Paul Cullen
1Department of Microbiology and Immunology, University at Buffalo, State University of New York, 14215, USA.
Abstract:
Moraxella catarrhalis is an important cause of respiratory infections in adults with chronic obstructive pulmonary disease (COPD) and of otitis media in children. Outer membrane protein (OMP) G1a is an approximately 29-kDa surface lipoprotein and is a potential vaccine candidate. The gene that encodes OMP G1a was expressed and purified using a novel plasmid vector. [(3)H]palmitic acid labeling demonstrated that both native and recombinant OMP G1a contain covalently bound palmitic acid. To assess the expression of OMP G1a during human infection, paired sera and sputum supernatants from adults with COPD followed prospectively were studied by enzyme-linked immunosorbent assays with recombinant lipidated OMP G1a to detect antibodies made specifically during carriage of M. catarrhalis. Overall, 23% of patients developed either a serum immunoglobulin G (IgG) response (9%) or sputum IgA response (21%) to OMP G1a, following 100 episodes of acquisition and clearance of M. catarrhalis. Patients developed antibody responses at similar rates following episodes of clinical exacerbation compared to asymptomatic colonization. Serum IgG antibodies following natural infection were directed predominantly at OMP G1a epitopes that are not exposed on the bacterial surface. These data show that OMP G1a is expressed during infection of the human respiratory tract and is a target of systemic and mucosal antibodies. These observations indicate that OMP G1a, a highly conserved surface protein, should be evaluated further as a vaccine candidate.
Insights
Outer membrane protein G1a from Moraxella catarrhalis is expressed during respiratory infections and elicits antibody responses. This conserved protein is a promising candidate for developing new vaccines against bacterial infections.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Moraxella catarrhalis causes significant respiratory infections in adults with COPD and otitis media in children.
- Outer membrane protein (OMP) G1a is a surface lipoprotein of M. catarrhalis and a potential vaccine target.
Purpose of the Study:
- To investigate the expression of OMP G1a during human M. catarrhalis infections.
- To determine if OMP G1a elicits specific antibody responses in patients with COPD.
Main Methods:
- Recombinant OMP G1a was expressed and purified.
- Lipidated OMP G1a was used in ELISAs to detect serum IgG and sputum IgA in COPD patients during M. catarrhalis colonization.
- Antibody responses were correlated with infection episodes and clinical status.
Main Results:
- Recombinant OMP G1a was successfully produced and shown to be lipidated.
- Twenty-three percent of COPD patients developed antibody responses (serum IgG or sputum IgA) to OMP G1a.
- Antibody responses occurred similarly during asymptomatic colonization and clinical exacerbations.
- Antibodies targeted epitopes not exposed on the bacterial surface.
Conclusions:
- OMP G1a is expressed during M. catarrhalis respiratory tract infections.
- OMP G1a is a target of both systemic and mucosal immune responses.
- OMP G1a is a conserved surface protein with potential as a vaccine candidate.
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