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

Adlowitz, Diana G.; Hiltke, Thomas J.; Lesse, Alan J.; Murphy, Timothy F.

doi:10.1016/j.vaccine.2003.12.016

Vaccine

2004

DOI: 10.1016/j.vaccine.2003.12.016

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

Diana G. Adlowitz

Thomas J. Hiltke

Alan J. Lesse

et al.

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Cited by 22 publications

(23 citation statements)

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“…OMP G1a is present in all strains of M. catarrhalis studied thus far. In addition, sequence analysis of ompG1a from 25 clinical isolates of M. catarrhalis identifies the gene as being highly conserved among strains (1). These features indicate that OMP G1a is a candidate for further evaluation as a vaccine antigen.…”

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confidence: 95%

Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

et al. 2005

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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 ϳ29-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.Over the past 2 decades, Moraxella catarrhalis has emerged as an important human respiratory pathogen. Acquisition of a new strain of M. catarrhalis is associated with the development of an exacerbation in patients with chronic obstructive pulmonary disease (COPD) (43). Indeed, M. catarrhalis is the second most common bacterial cause of exacerbations in adults with COPD after nontypeable Haemophilus influenzae (32,38,44). COPD is the fourth-leading cause of death in the United States and is projected to rank fifth in the world by 2020 (2,26,28,39). M. catarrhalis is also the third-most-common bacterial cause of otitis media in children after Streptococcus pneumoniae and nontypeable H. influenzae (25). Approximately 25 million episodes of otitis media occur annually in the United States, and $2 billion is spent annually on treatment (25). It is estimated that M. catarrhalis causes 10% to 20% of cases of acute otitis media. Recurrent otitis media in infants and young children affects speech development and cognitive abilities (25, 42). Finally, M. catarrhalis is also a common cause of sinusitis in children and adults (32). Since M. catarrhalis is an important human pathogen for infants and adults with COPD, there is a need for a vaccine. Infants could be immunized to prevent otitis media and adults with COPD could be immunized to prevent exacerbations caused by M. catarrhalis.One approach to vaccine development for gram-negative bacteria has been to use outer membrane proteins (OMPs) as vaccine antigens. Effectiv...

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Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

et al. 2005

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“…Rabbit antiserum to OMP CD was produced in our laboratory according to a protocol described by Adlowitz et al (2).…”

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Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

2011

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Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.Moraxella catarrhalis is a Gram-negative diplococcus frequently found as a commensal of the upper respiratory tract (14,19). However, over the past 2 to 3 decades this bacterium has shifted from being considered a harmless commensal to being recognized as a genuine respiratory tract pathogen of serious public health concern (34, 54).Acute otitis media is the most common bacterial infection in children, with 70% experiencing at least one episode by age 3 (53). M. catarrhalis is the third leading cause of otitis media after Streptococcus pneumoniae and nontypeable Haemophilus influenzae (21,34). M. catarrhalis is associated with up to 25% of acute otitis media cases by culture (37) and 46.4% of chronic middle ear effusion cases by PCR (41). In addition, the nasopharyngeal carriage rate of M. catarrhalis in children is high (up to 75%) and the frequency of colonization is positively related to the development of otitis media (14).In adults, M. catarrhalis is the second most common bacterial cause of exacerbations of chronic obstructive pulmonary disease (COPD) after nontypeable H. influenzae (33,48,49). COPD is the fourth leading cause of death in the United States, affecting 24 million Americans (25, 26). M. catarrhalis causes approximately 10% of exacerbations of COPD, accounting for 2 to 4 million episodes annually (33). Furthermore, M. catarrhalis also colonizes the lower respiratory tract in up to 2.5 to 10% of adults with COPD at their stable states (31, 59). Lower airway colonization contributes to airway inflammation in COPD as a result of sloughing of highly inflammatory bacterial cell wall antigens into the airway (49).The significant clinical implications of M. catarrhalis require a vaccine targeting bo...

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“…An ideal vaccine candidate has several characteristics, including exposure on the bacterial surface, sequence conservation among strains, expression during human infection, and generation of a protective immune response. To date, a limited number of outer membrane proteins have been examined as potential vaccine antigens (1,4,11,16,17,21,28,37).…”

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Mining the Moraxella catarrhalis Genome: Identification of Potential Vaccine Antigens Expressed during Human Infection

Ruckdeschel¹,

Kirkham²,

Lesse

et al. 2008

Infect Immun

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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.

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

Cited by 22 publications

References 27 publications

Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen

Mining the Moraxella catarrhalis Genome: Identification of Potential Vaccine Antigens Expressed during Human Infection

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