Human immune response to Pseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine

Pier, Gerald B.; Desjardin, Dennis E.; Grout, Martha; Garner, Carol; Bennett, Susan E.; Pekoe, Gary; Fuller, Steven A.; Thornton, Mark; Harkonen, W. Scott; Miller, Harold C.

doi:10.1128/iai.62.9.3972-3979.1994

Cited by 77 publications

(27 citation statements)

References 35 publications

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“…It is well known that Pseudomonas aeruginosa forms bio®lms on natural surfaces, medical biomaterials and CF (cystic ®brosis) lung epithelial cells (Costerton et al 1987;Christensen and Characklis 1990;Pier et al 1994). The ability to express numerous different adhesins enables these organisms to¯ourish under diverse conditions.…”

Section: Discussionmentioning

confidence: 99%

Alterations in extracellular substances during the biofilm development of Pseudomonas aeruginosa on aluminium plates

et al. 2000

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The chemical moieties during bio®lm formation of Pseudomonas aeruginosa on aluminium plates were examined for a period of 17 days. The effect of¯uid shearing upon bio®lm formation has also been investigated. The Fourier transform infrared (FTIR) spectrum of the bio®lm taken on the ®fth day showed signi®cant differences compared with the spectrum of the unattached bacterial cells, indicating that structural changes or modi®cations of the cell envelope had taken place during the development of the bio®lm. Major changes were also observed in the spectrum during the subsequent development of the bio®lm from day 5 to day 17. The increasing intensity of a band corresponding to the symmetric stretching mode of the carboxyl group indicated interactions between the carboxyl group and the aluminium surface. Increased bacterial colonization was also observed at the air±water interface of the aluminium plates when compared with the middle and the bottom parts. Changes in FTIR spectra of the bio®lm at the bottom, at the middle, and at the air±water interface suggest that the mechanisms of bacterial attachment differed by a ±COO ± interaction at the air± water interface, and by both ±COO ± and NH 3 groups beneath the water surface.

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Section: Discussionmentioning

confidence: 99%

Alterations in extracellular substances during the biofilm development of Pseudomonas aeruginosa on aluminium plates

et al. 2000

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“…In the two preparations of alginate vaccines that they used to immunize human volunteers, designated Lot 1 and Lot 2, they found Lot 1 to be lowly immunogenic. Lot 2 which has a larger average size of alginate polymers, when used at an optimal dose of 100 Wg elicited long-lived opsonic antibodies in 80^90% of the vaccinated individuals [67].…”

Section: Antigens Of Extracellular Slime Polysaccharide (Alginate)mentioning

confidence: 99%

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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“…The two main causes of shifting from non‐mucoid to mucoid variants has been identified as the lack of sufficient oxygen in the mucus and the release of reactive oxygen species from polymorphonuclear cells (PMNs) in the lung . Several studies showed that alginate elicits opsonic antibodies and has conserved epitopic sites in the most mucoid strains . The safety of alginate has been proven at various dosages by some human trials , and a direct relationship between the molecular size of alginate and the induction of opsonic antibodies has been observed .…”

mentioning

confidence: 99%

“…Several studies showed that alginate elicits opsonic antibodies and has conserved epitopic sites in the most mucoid strains . The safety of alginate has been proven at various dosages by some human trials , and a direct relationship between the molecular size of alginate and the induction of opsonic antibodies has been observed . In spite of the safety of alginate as a vaccine candidate to confer immunity against P. aeruginosa infection, it does not have sufficient immunogenicity to provoke long‐lived opsonic antibodies .…”

mentioning

confidence: 99%

“…The safety of alginate has been proven at various dosages by some human trials , and a direct relationship between the molecular size of alginate and the induction of opsonic antibodies has been observed . In spite of the safety of alginate as a vaccine candidate to confer immunity against P. aeruginosa infection, it does not have sufficient immunogenicity to provoke long‐lived opsonic antibodies . The most successful method to overcome this issue and increase the immunogenicity of alginate is conjugation, whereby surface polysaccharides are conjugated to a carrier protein .…”

mentioning

confidence: 99%

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Immunological evaluation of an alginate‐based conjugate as a vaccine candidate against Pseudomonas aeruginosa

Farjah

Owlia

Siadat

et al. 2014

APMIS

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Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, is usually resistant to antimicrobial agents, and is the leading cause of morbidity and premature mortality in patients with cystic fibrosis (CF). Mucoid strains of P. aeruginosa produce a virulence factor known as alginate. Developing a strategy to raise opsonic antibodies against alginate could be promising for the treatment of P. aeruginosa infection in CF patients. Conjugation of alginate to a carrier protein is a good method for increasing the immunogenicity of alginate. We conjugated alginate to the outer membrane vesicle (OMV) of Neisseria meningitidis serogroup B, which is a safe carrier protein, and evaluated its efficacy in mice. To evaluate the immune response, total IgG, IgG1, IgG2a, and IgG2b titers were analyzed. Immunization of mice with the alginate-OMV conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intranasally with P. aeruginosa. Further studies showed that the conjugated vaccine could eliminate P. aeruginosa from the lungs of infected mice. This study supports the proposal that immunization of mice with an alginate-OMV conjugate vaccine could be safe and protective against P. aeruginosa infection.

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Human immune response to Pseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine

Cited by 77 publications

References 35 publications

Alterations in extracellular substances during the biofilm development of Pseudomonas aeruginosa on aluminium plates

Alterations in extracellular substances during the biofilm development of Pseudomonas aeruginosa on aluminium plates

Pseudomonas aeruginosa antigens as potential vaccines

Immunological evaluation of an alginate‐based conjugate as a vaccine candidate against Pseudomonas aeruginosa

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