Vaccine development for<i>Moraxella catarrhalis</i>: rationale, approaches and challenges

Murphy, Timothy F.

doi:10.1586/erv.09.28

Cited by 17 publications

(25 citation statements)

References 28 publications

(18 reference statements)

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“…In evaluating vaccine antigens, the ideal one should meet several characteristics: (i) present on the surface of all strains, (ii) antigenically conserved among strains, and (iii) capable of inducing a protective immune responses (4,49). In this study, we showed that SBP2 has excellent potential as a vaccine antigen against M. catarrhalis, having essentially all of these characteristics.…”

Section: Discussionmentioning

confidence: 82%

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Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

et al. 2014

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Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-g and 50-g doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis.

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Section: Discussionmentioning

confidence: 82%

“…The mouse pulmonary clearance model is the most widely used model to test potential vaccine antigens of M. catarrhalis (4,49). Subcutaneous immunization of mice with purified recombinant SBP2 induced enhanced pulmonary clearance following aerosol pulmonary challenge (Fig.…”

Section: Discussionmentioning

confidence: 99%

Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

et al. 2014

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“…Further, M. catarrhalis is the second most common cause of exacerbations of COPD after H. influenzae; it is responsible for 10 to 15% of the exacerbations and annually causes 2 to 4 million episodes in the United States (47,60). Antibiotics are widely used for treatment of OM, but the high prevalence of this disease and the increasing incidence of antibiotic-resistant strains mean that multivalent vaccines, preferably vaccines with protective antigens for all three causative bacterial agents, must be developed (46).…”

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confidence: 99%

Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen

et al. 2010

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Moraxella catarrhalis is an emerging human-restricted respiratory tract pathogen that is a common cause of childhood otitis media and exacerbations of chronic obstructive pulmonary disease in adults. Here, we report the first completely assembled and annotated genome sequence of an isolate of M. catarrhalis, strain RH4, which originally was isolated from blood of an infected patient. The RH4 genome consists of 1,863,286 nucleotides that form 1,886 protein-encoding genes. Comparison of the RH4 genome to the ATCC 43617 contigs demonstrated that the gene content of both strains is highly conserved. In silico phylogenetic analyses based on both 16S rRNA and multilocus sequence typing revealed that RH4 belongs to the seroresistant lineage. We were able to identify almost the entire repertoire of known M. catarrhalis virulence factors and mapped the members of the biosynthetic pathways for lipooligosaccharide, peptidoglycan, and type IV pili. Reconstruction of the central metabolic pathways suggested that RH4 relies on fatty acid and acetate metabolism, as the genes encoding the enzymes required for the glyoxylate pathway, the tricarboxylic acid cycle, the gluconeogenic pathway, the nonoxidative branch of the pentose phosphate pathway, the beta-oxidation pathway of fatty acids, and acetate metabolism were present. Moreover, pathways important for survival under challenging in vivo conditions, such as the iron-acquisition pathways, nitrogen metabolism, and oxidative stress responses, were identified. Finally, we showed by microarray expression profiling that ϳ88% of the predicted coding sequences are transcribed under in vitro conditions. Overall, these results provide a foundation for future research into the mechanisms of M. catarrhalis pathogenesis and vaccine development.Moraxella catarrhalis is an emerging human-restricted unencapsulated Gram-negative mucosal pathogen. Long considered to be a commensal of the upper respiratory tract, this bacterium has now firmly been established to be an etiological cause of otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). It is the third most common cause of childhood OM after Haemophilus influenzae and Streptococcus pneumoniae (37, 64), and it is responsible for up to 20% of the cases (64, 65). Further, M. catarrhalis is the second most common cause of exacerbations of COPD after H. influenzae; it is responsible for 10 to 15% of the exacerbations and annually causes 2 to 4 million episodes in the United States (47, 60). Antibiotics are widely used for treatment of OM, but the high prevalence of this disease and the increasing incidence of antibiotic-resistant strains mean that multivalent vaccines, preferably vaccines with protective antigens for all three causative bacterial agents, must be developed (46).M. catarrhalis is able to colonize the mucosal surfaces of the middle ear in OM patients and the lower respiratory tract in COPD patients (31,60). Successful colonization of the human host is a complex process which requires the expression ...

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“…The current vaccine studies have mostly focused on various outer membrane proteins (OMPs) as vaccine candidates. To date, a limited number of OMPs have been examined and are currently under different stages of evaluation as part of an effort to develop a multicomponent vaccine against M. catarrhalis (27,32,51). To search for more vaccine candidates in an efficient way, a genome mining approach generated a pool of 348 open reading frames (ORFs) as potential surface proteins (44).…”

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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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Vaccine development forMoraxella catarrhalis: rationale, approaches and challenges

Cited by 17 publications

References 28 publications

Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

Genome Analysis of Moraxella catarrhalis Strain RH4, a Human Respiratory Tract Pathogen

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

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