Generation and characterization of murine antiflagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa

Rosok, M J; Stebbins, M. R.; Connelly, Katherine R. S.; Lostrom, Mark E.; Siadak, Anthony W.

doi:10.1128/iai.58.12.3819-3828.1990

Cited by 46 publications

(16 citation statements)

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“…Using liquid chromatography, we were able to isolate nine proteins from the OM and these were sub- Table 8 Localization of speci¢c antigens (epitopes) in P. aeruginosa and current status of results from characterization and protective property studies Cell structure or localization Speci¢c antigen (epitope) Characterization References Flagella H-antigens Protein (£agellin) serovar-speci¢c antigens, H1-and H2-epitopes (partial antigens), protective antigens [73,185,187,188] Pili Antigens Protein-(pilin, one polypeptide chain) speci¢c antigens [189,191,193] Cytoplasmic : Ribosomes Antigen(s) RNA-protein complex as protective antigen, speci¢c ribosomal vaccine developed, contamination by LPS could be a concern…”

Section: Outer Membrane Protein Antigensmentioning

confidence: 99%

“…Rosok et al [189] produced two murine monoclonal antibodies, belonging to IgG3 and IgG2a isotypes, that bind to P. aeruginosa type a £agella and type b £agella respectively. Speci¢city of each monoclonal antibody for type a or type b £agella was demonstrated using ELISA, indirect immuno£uorescence, and immunoblotting.…”

Section: Flagellar H-antigens Serotyping Of P Aeruginosa P Aeruginosamentioning

confidence: 99%

“…Anti-£agella sera caused an inhibition of the motility of organisms and protected mice against P. aeruginosa burn wound sepsis. The anti-£agella antibodies provided speci¢c and signi¢cant prophylactic and therapeutic protection against lethal challenge with P. aeruginosa strains [189]. However, the role H-antigen(s) plays in the induction of host protective immunity is disputable.…”

Section: Flagellar H-antigens Serotyping Of P Aeruginosa P Aeruginosamentioning

confidence: 99%

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Pseudomonas aeruginosa antigens as potential vaccines

Stanislavsky

1997

FEMS Microbiology Reviews

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Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting predominantly of alginate, was found to be heterogeneous in terms of size and immunogenicity. High molecular mass alginate components (30^300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10^30 kDa) possess conserved epitopes in addition to unique epitopes. Surface-exposed antigens including Oantigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce crossprotective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti-P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensit...

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Section: Outer Membrane Protein Antigensmentioning

confidence: 99%

Section: Flagellar H-antigens Serotyping Of P Aeruginosa P Aeruginosamentioning

confidence: 99%

Section: Flagellar H-antigens Serotyping Of P Aeruginosa P Aeruginosamentioning

confidence: 99%

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Pseudomonas aeruginosa antigens as potential vaccines

Stanislavsky

1997

FEMS Microbiology Reviews

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“…Rosok et al [189]produced two murine monoclonal antibodies, belonging to IgG3 and IgG2a isotypes, that bind to P. aeruginosa type a flagella and type b flagella respectively. Specificity of each monoclonal antibody for type a or type b flagella was demonstrated using ELISA, indirect immunofluorescence, and immunoblotting.…”

Section: Flagellar H‐antigens Serotyping Of P Aeruginosamentioning

confidence: 99%

“…Anti‐flagella sera caused an inhibition of the motility of organisms and protected mice against P. aeruginosa burn wound sepsis. The anti‐flagella antibodies provided specific and significant prophylactic and therapeutic protection against lethal challenge with P. aeruginosa strains [189]. However, the role H‐antigen(s) plays in the induction of host protective immunity is disputable.…”

Section: Flagellar H‐antigens Serotyping Of P Aeruginosamentioning

confidence: 99%

Pseudomonas aeruginosaantigens as potential vaccines

Stanislavsky

Lam

1997

FEMS Microbiol Rev

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Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting predominantly of alginate, was found to be heterogenous in terms of size and immunogenicity. High molecular mass alginate components (30-300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10-30 kDa) possess conserved epitopes in addition to unique epitopes. Surface-exposed antigens including O-antigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce cross-protective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti-P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensitive. Res...

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Flagella and Pili ofPseudomonas aeruginosa

Jyot

Ramphal

2008

Pseudomonas

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IntroductionMotility is one of the most impressive features of microbial life and requires a large percent of cellular energy. Its roles include increased efficiency of nutrient acquisition, evasion of toxic substances, ability to translocate to preferred hosts and access to optimal colonization sites within them, as well as dispersal in the environment. Movement in aqueous environments by swimming or along surfaces by using different modes of translocation has been classified into several distinct types [1]. Pseudomonas aeruginosa exhibits three types of motility -flagellum-mediated swimming, flagellum and type IVpilus-mediated swarming [2,3], and type IVpilus-mediated twitching [4][5][6]. Swarming motility can be distinguished from swimming motility in that swarming is required to move across a hydrated, viscous semisolid surface, while swimming allows movement through a relatively low-viscosity liquid environment. The direction of movement is biased by chemotactic responses to chemical stimuli [7][8][9]. This chapter focuses on the two motility organelles of P. aeruginosa, i.e. the flagellum and the pilus, their structure, regulation and role in pathogenesis. 4.2 Flagellum of P. aeruginosa P. aeruginosa has a single, unsheathed polar flagellum similar to that of Caulobacter crescentus and Vibrio parahaemolyticus, but unlike the polar, sheathed flagellum observed in Helicobacter and the peritrichous flagella seen in Escherichia coli and Salmonella enterica serovar Typhimurium. However, swarmer cells of P. aeruginosa appear to possess on average two polar flagella and no lateral flagella [2,10]. At the genetic level, the expression of flagellar genes in P. aeruginosa is tightly regulated, involving transcriptional activators and multiple s factors as in other enteric bacteria. Flagellar structural genes are usually conserved across the genomes Pseudomonas. Model Organism, Pathogen, Cell Factory. Edited by Bernd H.A. Rehm

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Generation and characterization of murine antiflagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa

Cited by 46 publications

References 48 publications

Pseudomonas aeruginosa antigens as potential vaccines

Pseudomonas aeruginosa antigens as potential vaccines

Pseudomonas aeruginosaantigens as potential vaccines

Flagella and Pili ofPseudomonas aeruginosa

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