Isolation and Characterization of Antigenic Components of a New Heptavalent Pseudomonas Vaccine

Hanessian, Stephen; Regan, W. M.; Watson, Donald.; Haskell, Theodore H.

doi:10.1038/newbio229209a0

Cited by 94 publications

(38 citation statements)

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“…We examined the concentration of antibody to IT-2 PS in the acute- We believe that the development of an immunogenic form of the 0-specific side chain that can be administered without significant toxicity constitutes a major step towards development of a P. aeruginosa vaccine. Numerous animal studies (9,27) have demonstrated that antibody specific for serotype antigens such as high molecular weight PS are protective against P. aeruginosa infection. Previous attempts to vaccinate humans with P. aeruginosa LPS were hampered by the toxicity ofthis vaccine (12).…”

Section: Resultsmentioning

confidence: 99%

“…Research to date revealed that humoral immune responses after infection with P. aeruginosa are directed at serotype antigens (7,8). Animal studies using LPS vaccines have demonstrated a protective effect of type-specific antibody (9). There is an association between high levels of type-specific antibody in acute-phase serum and survival from P. aeruginosa sepsis (10, 1 1).…”

Section: Introductionmentioning

confidence: 99%

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Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide.

Pier¹,

Bennett²

1986

J. Clin. Invest.

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We analyzed high molecular weight polysaccharide (PS) from the Fisher immunotype 2 (IT-2) strain of Pseudomonas aeruginosa for molecular composition and structure, then determined its immunogenicity in healthy adults. The PS was composed of 2-acetamido-2,6-dideoxygalactose (N-acetyl fucosamine) and glucose in a molar ratio of 2:1. Structural analysis by carbon-13 and proton nuclear magnetic resonance confirmed that the high molecular weight PS was structurally identical to that of the 0-specific side chain of the lipopolysaccharide. PS differed from this material in molecular size. Immunization of 19 adult volunteers with doses of 50-100 ,ug of PS resulted in significant rises (P < 0.04-P < 0.0001) in binding antibody levels and killing antibody titers 2 and 4 wk postimmunization. The only reaction to the vaccine was localized tenderness at the immunization site. Analysis of the immunoglobulin isotype response to the vaccine showed a rise in specific serum IgG and IgA antibodies. Heterologous responses to other P. aeruginosa PS antigens were not seen. The antibody levels attained by vaccination were comparable with those in acute-phase serum samples of patients who survived sepsis with IT-2 P. aeruginosa and were significantly higher (P < 0.03) than specific antibody levels in bacteremic patients who died. These results confirm that PS is a high molecular weight, immunogenic form of the P. aeruginosa IT-2 serotype antigen, eliciting levels of type-specific antibody comparable with those seen among patients surviving an episode of P. aeruginosa sepsis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide.

Pier¹,

Bennett²

1986

J. Clin. Invest.

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“…The LPS antigen employed was the Parke-Davis vaccine containing the seven Fisher-Devlin serotype-specific immunodeterminants (22). Polyvinylchloride microtiter plate wells (Dynatech, Alexandria, VA) were coated with 20 pg/ml PA LPS in normal saline for 1 h at 37" C and aspirated.…”

Section: Serum Pa Lps Igg Antibodies Serum Levels Of Igg Antibodiesmentioning

confidence: 99%

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

et al. 1986

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ABSTRACT'. Patients with cystic fibrosis (CF) whose respiratory tracts are colonized with Pseudomonas aeruginosa (PA) may develop a specific opsonic deficiency for alveolar macrophage phagocytosis of PA. We examined the possible role of altered antibody (Ab) isotype in this phenomenom by measuring serum levels and distribution of IgG and IgG subclass Ab (IgGl, IgG2, IgG3, and IgG4) to the major opsonic immunodeterminant, serotype-specific lipopolysaccharide (LPS), by means of enzyme-linked immunosorbent assays employing monoclonal secondary antibodies, and comparing these results to the serum opsonic capacity in an in vitro murine alveolar macrophage phagocytic assay. Twenty-one patients with CF who were colonized with PA had approximately a 30-fold elevation of PA LPS IgG Ab levels and higher IgG subclass 1-4 Ab compared to 10 uncolonized patients with CF and 11 healthy controls (p < 0.05-0.0005 depending on the isotype). Colonized patients with CF had a shift in PA LPS Ab distribution toward IgG3 compared to uncolonized patients with CF (p < 0.02). A surprising finding was that uncolonized patients with CF had lower levels (p < 0.05) and proportion (p < 0.002) of PA LPS IgG2 Ab than controls, with an apparent shift to higher levels and proportion of PA LPS IgG4 (p < 0.01). Serum from colonized patients with CF showed diminished opsonic capacity for phagocytosis of PA compared to uncolonized patients and controls (p < 0.005), with 42% showing inhibitory activity.

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“…LPS also reported to activate NLRP3 when administered in the presence of ATP (Stutz, Golenbock, & Latz, 2009), as well as NLRP2 (Lamkanfi, & Dixit, 2009). A number of LPS vaccines have been investigated for use in CF patients in phase II and III clinical trials; however, these have not been successful (Doring & Pier, 2008;Hanessian, Regan, Watson, & Haskell, 1971;Langford & Hiller, 1984;Pennington, 1979;Pennington & Miler, 1979). The LPS based vaccines provided little immunity and did not appear to protect the patients from infection with P. aeruginosa (Pier, 2003).…”

Section: Lipopolysaccharidementioning

confidence: 99%

Pseudomonas aeruginosa – Pathogenesis and Pathogenic Mechanisms

Alhazmi

2015

IJB

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Pseudomonas aeruginosa is a common bacterium, Gram-negative opportunistic pathogen capable of infecting humans with compromised natural defenses and causing severe pulmonary disease. It is one of the leading pathogen associated with nosocomial infections. It has a vast arsenal of pathogenicity factors that are used to interfere with host defenses. Pathogenesis in P. aeruginosa facilitates adhesion, modulate or disrupt host cell pathways, and target the extracellular matrix. The propensity of P. aeruginosa to form biofilms further protects it from antibiotics and the host immune system. P. aeruginosa is intrinsically resistant to a large number of antibiotics and can be acquired resistance to many others, making treatment difficult. P. aeruginosa provokes a potent inflammatory response during the infectious process. The majority of mortalities in immunocompromised patients; cystic fibrosis, can be attributed to the progressive decline of lung function resulting from chronic infection by pathogens such as P. aeruginosa. Antibiotic treatment of chronic P. aeruginosa infections may temporarily suppress symptoms; however, they do not eradicate the pathogen. Lung diseases caused by P. aeruginosa are a leading cause of death in immunocompromised individuals as well as in children. Although immunocytes recruitment is critical to augment the host defense, excessive neutrophil accumulation results in life-threatening diseases, such as acute lung injury, as well as acute respiratory distress syndrome. Several virulence factors have been studied for their roles as potential vaccine candidate, although there is currently no clinically accepted vaccine. Understanding host-pathogen interaction is critical for the development of effective therapeutic strategies to control the damage in the lung.

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Isolation and Characterization of Antigenic Components of a New Heptavalent Pseudomonas Vaccine

Cited by 94 publications

References 5 publications

Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide.

Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide.

Altered Antibody Isotype in Cystic Fibrosis. Possible Role in Opsonic Deficiency

Pseudomonas aeruginosa – Pathogenesis and Pathogenic Mechanisms

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