A Large, Antigenically Conserved Protein On The Surface Of Moraxella Catarrhalis Is A Target For Protective Antibodies

Helminen, Merja; Maciver, Isobel; Latimer, Jo L.; Klesney-Tait, Julia; Cope, Leslie D.; Paris, Maria; McCracken, George H.; Hansen, Eric J.

doi:10.1093/infdis/170.4.867

Cited by 98 publications

(119 citation statements)

References 30 publications

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“…This sequence contains the epitope for the protective mAb 17C7, for which there is universal reactivity (16,83). In a mouse model, passive immunization with mAb 17C7 provided protection and improved pulmonary clearance of M. catarrhalis (83).…”

Section: Discussionmentioning

confidence: 99%

Immune Evasion ofMoraxella catarrhalisInvolves Ubiquitous Surface Protein A-Dependent C3d Binding

Hallström

Nordström

Tan

et al. 2011

The Journal of Immunology

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The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1299–452 and UspA2165–318. The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation.

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Section: Discussionmentioning

confidence: 99%

Immune Evasion ofMoraxella catarrhalisInvolves Ubiquitous Surface Protein A-Dependent C3d Binding

Hallström

Nordström

Tan

et al. 2011

The Journal of Immunology

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“…Incubation of HMW-OMP in formic acid produces a single band with a molecular mass of 120 to 140 kDa, suggesting that the HMW-OMP is an oligomer composed of several monomers (101). Analysis with monoclonal antibodies has established that the HMW-OMP contains epitopes on the bacterial surface (84,101). Furthermore, passive immunization of mice with a monoclonal antibody to the protein enhanced pulmonary clearance of B. catarrhalis (84).…”

Section: Outer Membrane Proteinsmentioning

confidence: 99%

“…Analysis with monoclonal antibodies has established that the HMW-OMP contains epitopes on the bacterial surface (84,101). Furthermore, passive immunization of mice with a monoclonal antibody to the protein enhanced pulmonary clearance of B. catarrhalis (84).…”

Section: Outer Membrane Proteinsmentioning

confidence: 99%

Lower respiratory tract infection

Sharland¹

2016

OSH Manual of Childhood Infections

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“…The major OMPs of M. catarrhalis are 98 to 20 kDa in size and have been named A to H (3, 16). In addition, a high-molecular-weight OMP of 300 to 700 kDa has been identified (12,14).CopB, an 81-kDa major OMP, has been a major focus of investigation (1,10,11). This protein is identical to OMP B2 (16, 21).…”

mentioning

confidence: 99%

“…The major OMPs of M. catarrhalis are 98 to 20 kDa in size and have been named A to H (3,16). In addition, a high-molecular-weight OMP of 300 to 700 kDa has been identified (12,14).…”

mentioning

confidence: 99%

Moraxella (Branhamella) catarrhalis

1994

JJPP

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Outer membrane protein (OMP) CopB, an iron-repressible 81-kDa major OMP of Moraxella (Branhamella) catarrhalis has been a major focus of investigation. To assess CopB as a potential vaccine antigen, we elucidated the degree of antigenic and sequence heterogeneity in this protein among strains of M. catarrhalis. Two monoclonal antibodies, 1F5 and 2.9F, which bind to surface-exposed epitopes on CopB recognized 60 and 70% of the strains, respectively. The degree of sequence heterogeneity in CopB was assessed by cloning and sequencing the CopB gene from two different strains of M. catarrhalis and comparing with the published sequence. There was 92 to 96% homology between the sequences at the nucleotide level and 90 to 95% homology at the amino acid level. The variability in the protein sequence is confined mainly to three moderately variable regions. Restriction fragment length polymorphism (RFLP) analysis of the CopB genes obtained from 20 diverse strains by PCR was performed. Ninety percent of the potential restriction sites in the constant regions and 47% of the potential restriction sites in the variable regions were present in the 20 strains, indicating that the pattern of variable and constant areas in the CopB gene is a general pattern among strains of M. catarrhalis. We conclude that the CopB gene is largely conserved among strains of M. catarrhalis and contains discrete regions which show moderate heterogeneity among strains.Moraxella (Branhamella) catarrhalis has emerged as an important human pathogen over the last two decades. In recent studies, it is the third most common bacterial pathogen isolated from the middle ear fluid of children with otitis media (2, 7). There has been a steady increase in the rate of isolation of M. catarrhalis from the sputum of adults with acute exacerbations of chronic obstructive pulmonary disease (9,15,18,19).The basic characteristics of the outer membrane proteins (OMPs) of M. catarrhalis have been well described. The major OMPs of M. catarrhalis are 98 to 20 kDa in size and have been named A to H (3, 16). In addition, a high-molecular-weight OMP of 300 to 700 kDa has been identified (12,14).CopB, an 81-kDa major OMP, has been a major focus of investigation (1,10,11). This protein is identical to OMP B2 (16, 21). The gene encoding this OMP has been cloned and sequenced from one strain (10). Though its precise function is not known, CopB is iron repressible and is involved in iron uptake by M. catarrhalis from lactoferrin and transferrin (1, 5).Several lines of evidence suggest that CopB is a potential vaccine antigen. In a murine model, a monoclonal antibody directed towards this OMP enhances clearance of M. catarrhalis from the lung (10). An isogenic mutant which does not express CopB has diminished ability to survive in the same murine pulmonary clearance model (11). This isogenic mutant also has diminished serum resistance to normal human sera in comparison to the wild type strain (11). To further assess CopB as a potential vaccine antigen, it will be important to know ...

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A Large, Antigenically Conserved Protein On The Surface Of Moraxella Catarrhalis Is A Target For Protective Antibodies

Cited by 98 publications

References 30 publications

Immune Evasion ofMoraxella catarrhalisInvolves Ubiquitous Surface Protein A-Dependent C3d Binding

Immune Evasion ofMoraxella catarrhalisInvolves Ubiquitous Surface Protein A-Dependent C3d Binding

Lower respiratory tract infection

Moraxella (Branhamella) catarrhalis

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