Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of
            <i>Moraxella catarrhalis</i>

Adlowitz, Diana G.; Sethi, Sanjay; Cullen, Paul; Adler, Ben; Murphy, Timothy F.

doi:10.1128/iai.73.10.6601-6607.2005

Cited by 18 publications

(20 citation statements)

References 51 publications

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“…Variability among individuals in the surface bacterial antigens to which antibodies are directed is a hallmark of antibody responses to bacteria in the COPD setting (9,44,45). The proportion of patients who developed new antibody responses to Msp22, Msp75, and Msp78 observed in this study parallels the proportion observed for M. catarrhalis OMPs E, G1a, and G1b when similar methods were used (2,3,11). The observation that some patients with COPD developed new systemic and mucosal antibodies to Msp22, Msp75, and Msp78 in samples collected 1 month after clearance of M. catarrhalis compared to paired samples collected immediately before acquisition of the organism supports the conclusion that the proteins are expressed by M. catarrhalis in the human respiratory tract.…”

Section: Resultssupporting

confidence: 69%

“…To determine the cutoff value for a significant change between preacquisition and postclearance serum IgG and sputum IgA levels, 10 control pairs were examined using a previously described method (2,3,34,36). Control samples obtained 2 months apart (the same time interval used for the experimental samples) from patients whose sputum cultures were negative for M. catarrhalis were identified.…”

Section: Resultsmentioning

confidence: 99%

“…Cloning into these vectors resulted in fusion proteins expressing a six-His tag under the control of an isopropyl-␤-D-thiogalactosidase (IPTG)-inducible promoter. Additionally, the pCATCH plasmid was chosen for msp22, which encodes a putative lipoprotein, because this plasmid contains E. coli lipoprotein signal sequences that code for attachment of an N-terminal lipid moiety during processing, allowing expression of the msp22 protein with an amino-terminal lipid (3,18).…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…Therefore, antibodies to conformational epitopes that are denatured in SDS-PAGE will not be detected. Indeed, in other work using quantitative enzyme-linked immunosorbent assays with purified recombinant protein antigens, we have demonstrated the development of sputum IgA to other surface proteins of M. catarrhalis, including outer membrane proteins CD and G1a (1,16). Sputum IgA to these antigens was not detected by immunoblot assay in the present study, indicating the development of antibodies to conformational epitopes on the proteins.…”

Section: Discussioncontrasting

confidence: 38%

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

et al. 2005

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Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of wellcharacterized sputum supernatant samples from adults with COPD who had acquired and subsequently cleared M. catarrhalis from their respiratory tracts were studied in detail in an effort to begin to elucidate potentially protective immune responses. Flow cytometry analysis was used to study the distribution of immunoglobulin isotypes in paired preacquisition and postclearance sputum samples. The results showed that immunoglobulin A (IgA) is the predominant M. catarrhalis-specific immunoglobulin isotype and that the sputum IgA contains a secretory component, indicating that it is locally produced at the mucosal site. Chronic obstructive pulmonary disease (COPD) is a debilitating disease that is the fourth most common cause of death in the United States (2, 4). Bacteria play several potential roles in the course and pathogenesis of the disease (20). Selected bacteria colonize the lower airways of adults with COPD and release potent inflammatory molecules that contribute to the airway inflammation that is a hallmark of COPD (6,7,13,21,22). Patients with COPD acquire and clear bacteria from the respiratory tract continuously. Little is known about the immune responses that mediate this turnover of bacteria. The course of COPD is characterized by intermittent episodes of worsening of symptoms, known as exacerbations. It is estimated that approximately half of the exacerbations are caused by bacterial infection (20,23,24). Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most frequent bacterial causes of exacerbations of COPD (19,20).Studies involving the molecular typing of isolates recovered from sputum samples collected prospectively have begun to elucidate the dynamics of colonization and infection by M. catarrhalis in the setting of COPD (15). M. catarrhalis likely causes approximately 10% of exacerbations of COPD, accounting for approximately 2 to 4 million episodes annually. When adults with COPD acquire M. catarrhalis, the organism is cleared efficiently from the respiratory tract after a relatively short duration of carriage (median time, 34 days). Patients then develop strain-specific protection against reacquisition of the same strain (15). This observation that humans develop apparent protective responses to M. catarrhalis after clearing it from the respiratory tract provides the opportunity to begin to understand protective immune responses. The majority of patients develop serum immunoglobulin G (IgG) and/or sputum IgA responses to their homologous infecting isolate of M. catarrhalis, as demonstrated by whole-cell enzyme-linked immunosorbent assay and flow cytometry assays (3, 15). Further analysis of serum immunoglobulins in this cohort has revealed...

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“…Cloning of the oppA gene. The pCATCH plasmid is an expression vector engineered to express recombinant lipoprotein and has been used previously to express M. catarrhalis lipoproteins (3,11). The 1,967-bp oppA gene encoding the mature OppA protein was amplified from M. catarrhalis strain ATCC 43617 with primers P7 and P8 (Table 1) and ligated into pCATCH between restriction sites NcoI and BamHI.…”

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confidence: 99%

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

Cited by 18 publications

References 51 publications

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

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

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease

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

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