Evaluation of a 74-kDa transferrin-binding protein from Moraxella (Branhamella) catarrhalis as a vaccine candidate

Chen, Dexiang; McMichael, John; VanDerMeid, Karl R.; Masi, Amy W.; Bortell, Eric; Caplan, Jeffrey D.; Chakravarti, Deb N.; Barniak, Vicki

doi:10.1016/s0264-410x(99)00188-7

Cited by 19 publications

(10 citation statements)

References 34 publications

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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).…”

mentioning

confidence: 99%

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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mentioning

confidence: 99%

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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“…Immunization with UspA (7) or recombinant CD (40) enhanced pulmonary clearance of both homologous and heterologous strains in a murine challenge model. Other vaccine candidates such as TbpB and CopB elicit antibodies with bactericidal activity and promote clearance in the murine pulmonary model, however, they appeared in multiple serotypes (8,25). Further study with mapping of a protective epitope of the CopB is encouraging since a CopBrelated fusion protein elicited antibodies that reacted to both homologous and heterologous strains (1).…”

mentioning

confidence: 99%

Synthesis and Characterization of Lipooligosaccharide-Based Conjugate Vaccines for Serotype B Moraxella catarrhalis

2005

Infect Immun

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Moraxella catarrhalis is an important cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium that elicits bactericidal antibodies. Serological studies show that three major LOS types (A, B, and C) have been identified among clinical isolates. Our previous studies demonstrated that the type A LOS-based conjugates were immunogenic in animals. In this study, LOS from type B strain 26397 was detoxified and conjugated to tetanus toxoid (TT) or a cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight ratios were around 0.9. The antigenicity of the conjugates was similar to that of the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited a 180-to 230-fold rise of serum anti-LOS immunoglobulin G in mice and >2,000-fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated complement-mediated bactericidal activity against the homologous strain, and a representative rabbit antiserum showed bactericidal activity against nine of twelve clinical isolates studied. The bactericidal activity of the rabbit antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These results indicate that the type B LOS-based conjugates can be used as vaccine components for further investigation.Moraxella catarrhalis is a gram-negative diplococcus, currently the third leading cause of otitis media and sinusitis in children along with Streptococcus pneumoniae and nontypeable Haemophilus influenzae (4,5,15,17). Up to 80% of children below 3 years of age will be diagnosed with at least one episode of acute otitis media, and 15 to 20% of these middle-ear infections are caused by M. catarrhalis (18,43). Sinusitis, however, accounts for 5 to 10% of upper respiratory tract infections in early childhood (53). In addition, M. catarrhalis is a frequent cause of lower respiratory tract infections in the elderly, particularly in those with a compromised immune system or chronic obstructive pulmonary disease, where M. catarrhalis can cause severe infections such as pneumonia that can be life-threatening (44). Presently, treatment of the diseases has largely relied on antimicrobial agents. However, with growing antibiotic resistance observed in clinical isolates (34), attention has been focused on the possibility of vaccination against M. catarrhalis.

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“…The association of transferrin with the immune system derives from its ability to restrict serum free-iron levels, creating low-iron environments where the infection capacity of pathogenic microorganisms is limited [34,35]. Humoral innate immunity is mediated by soluble factors that inhibit microorganism growth [36].…”

Section: Transferrin As Antimicrobial Agentmentioning

confidence: 99%

Transferrin in fishes: A review article

Asmamaw¹

2016

J Coast Life Med

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Evaluation of a 74-kDa transferrin-binding protein from Moraxella (Branhamella) catarrhalis as a vaccine candidate

Cited by 19 publications

References 34 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

Synthesis and Characterization of Lipooligosaccharide-Based Conjugate Vaccines for Serotype B Moraxella catarrhalis

Transferrin in fishes: A review article

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