Immunization with Pseudomonas aeruginosa high-molecular-weight polysaccharides prevents death from Pseudomonas burn infections in mice

Pollack, Matthew; Pier, Gerald B.; Prescott, Richard K.

doi:10.1128/iai.43.2.759-760.1984

Cited by 22 publications

(6 citation statements)

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“…The relevance of these issues is emphasized by recent studies that have evaluated the functional activities of antibodies induced by LPS-derived Pseudomonas vaccines solely on the basis of testing carried out against vaccine strains. In some cases, these strains represent only one of multiple subtypes from a given serogroup (3,8,(30)(31)(32)38). It is unclear from such studies whether the 0-antigen-based vaccines in question are capable of eliciting functional antibody responses to all or only some of the subtypes which make up particular major serogroups.…”

Section: Edumentioning

confidence: 99%

“…Protective immunity against infections caused by Pseudomonas aeruginosa is mediated by antibodies to the O-polysaccharide portion of lipopolysaccharides (LPS) residing in the bacterial outer membrane. This has been documented in animal models (3,4,26,33,38,50) and in humans (40,47,48). LPS-based vaccines can prevent human Pseudomonas infections (13,14,49), although the use of such vaccines may be associated with local and systemic toxicity.…”

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Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06

et al. 1994

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Structural and antigenic heterogeneity has been noted among lipopolysaccharides (LPS) produced by Pseudomonas aeruginosa within serogroups previously considered to be serologically homogeneous. We characterized murine monoclonal antibodies (MAbs) and immunization-induced human polyclonal antibodies reactive with one or more of five structurally variant LPS subtypes belonging to serogroup 06 of the International Antigenic Typing System. Analyses of five different MAbs employing purified LPS or whole bacteria in enzyme-linked immunosorbent assays and Western blot (immunoblot) assays revealed five distinct patterns of subtype specificity, ranging from recognition of a single subtype to reactivity with all five. MAb-mediated opsonophagocytic killing and in vivo protection against live challenge in mice correlated, in general, with differential binding to various LPS subtypes. In comparison, sera from human vaccinees immunized with LPS-derived high-molecular-weight polysaccharide from P. aeruginosa Fisher immunotype 1, one of five serogroup 06 subtypes, exhibited LPS binding and opsonic activity against all five subtypes. Antibodies in the human sera effectively inhibited binding to all five LPS subtype antigens of the cross-reactive MAb, LC3-2H2, suggesting the existence of a common serogroup-related epitope. These findings emphasize the importance of defining subtype-associated variations in LPS antigenicity and corresponding differences in antibody specificity and function as a basis for designing immunoprophylactic or therapeutic strategies which target P. aeruginosa LPS.

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Section: Edumentioning

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Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06

et al. 1994

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“…Detoxification of LPS by acid hydrolysis to eliminate the lipid A portion and isolation of the immunogenic high-molecular-weight polysaccharide O antigens, originally described in 1978 (33,35), have consistently resulted in monovalent preparations of O antigens that are immunogenic in mice (30,31,34,35) and humans (26,28). These antigens elicit protective immunity in a variety of animal models (23,29,30,31,37) when the challenge strain is the one from which the immunogen was obtained. However, combining multiple high-molecular-weight O polysaccharides into one heptavalent preparation has resulted in only limited levels of opsonic antibodies to nonvaccine strains.…”

Section: Discussionmentioning

confidence: 99%

“…To develop safe and effective O-antigen-specific P. aeruginosa vaccines, we have utilized the high-molecular-mass (Ͼ100,000-Da) fraction of O polysaccharides. These antigens are safe and immunogenic in humans and animals (13,27,37) and elicit protective antibodies to the strains from which they are isolated. However, in recent studies of animals immunized with a heptavalent high-molecular-weight O-polysaccharide vaccine whose individual components were isolated from single strains representative of the major serogroups causing P. aeruginosa infection, opsonic antibody responses to the groupspecific antigens were not commonly elicited (13).…”

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Complex Serology and Immune Response of Mice to Variant High-Molecular-Weight O Polysaccharides Isolated from Pseudomonas aeruginosa Serogroup O2 Strains

Hatano

Pier

1998

Infect Immun

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The O antigen of the Pseudomonas aeruginosalipopolysaccharide is the optimal target for protective antibodies, but the unusual and complex nature of their sugar substituents has made it difficult to define the range of these structures needed in an effective vaccine. Most clinical isolates of P. aeruginosacan be classified into 10 O-antigen serogroups, but slight chemical differences among O polysaccharides within a serogroup give rise to subtype epitopes. These epitopes could impact the reactivity of O-antigen-specific antibodies, as well as the susceptibility of a target strain to protective, opsonic antibodies. To define parameters of serogroup and subtype-epitope immunogenicity, antigenicity, and surface expression on P. aeruginosa cells, we prepared high-molecular-weight O-polysaccharide vaccines from strains ofP. aeruginosa serogroup O2, for which eight structurally variant O antigens expressing six defined subtype epitopes (O2a to O2f) have been identified. A complex pattern of immune responses to these antigens was observed following vaccination of mice. The high-molecular-weight O polysaccharides were generally more immunogenic at low doses (1 and 10 μg) than at a high dose (50 μg) and usually elicited antibodies that opsonized the homologous strain for phagocytic killing. Some of the individual polysaccharides elicited cross-opsonic antibodies to a variable number of strains that express all of the defined serogroup O2 subtype epitopes. Combination into one vaccine of two antigens that individually elicited cross-reactive opsonic antibodies to most members of the O2 serogroup inhibited, instead of enhanced, the production of antibodies broadly reactive with most serogroup O2 subtype strains. Thus, immune responses to P. aeruginosa O antigens may be restricted to a limited range of epitopes on structurally complex O antigens, and combining multiple related antigens into a single vaccine formulation may inhibit the production of those antibodies best able to protect against mostP. aeruginosa strains within a given O-antigen serogroup.

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“…Each extract number corresponds to the IATS serotype from which the extract is derived, with the exception that extract 14 is obtained from IATS serotype 17. The anode is to the left and top of all immunoplates.VOL 51,. 1986 s.E on October 6, 2020 by guest http://iai.asm.org/ Downloaded from…”

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Immunochemical and biochemical analysis of the polyvalent Pseudomonas aeruginosa vaccine PEV

MacIntyre¹,

McVeigh²,

Owen³

1986

Infect Immun

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were subjected to biochemical analysis and to detailed immunochemical analysis with rabbit anti-PEV immunoglobulins. The results of chemical analysis, of analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed in coajunction with silver staining, and of analysis by crossed immunoelectrophoresis, sodium dodecyl sulfate-polyacrylamide gel-crossed immunoelectrophoresis, and Western blotting showed clearly that lipopolysaccharide was a major constituent of each monovalent extract and that it was probably the dominant antigen present in at least 15 of the 16 monovalent extracts. A 16.2-kilodalton protein, which was pronase resistant and nonsedimentable at 105,000 x g and which appeared to be biochemically and antigenically unrelated to pili, was a common although minor antigen for all extracts. Several other proteins, some of outer membrane origin, were also detected in unformalinized extracts, but these were also minor antigenic constituents of the vaccine. Neither pilin nor flagellin appeared to be major protein constituents of tested monovalent extracts, although anti-flagella antibodies could be demonstrated in rabbit anti-PEV by Western blotting. Preliminary analysis by crossed immunoelectrophoresis of serum raised in volunteers to PEV also indicated the presence therein of antibodies to lipopolysaccharide antigens.

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Immunization with Pseudomonas aeruginosa high-molecular-weight polysaccharides prevents death from Pseudomonas burn infections in mice

Cited by 22 publications

References 9 publications

Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06

Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06

Complex Serology and Immune Response of Mice to Variant High-Molecular-Weight O Polysaccharides Isolated from Pseudomonas aeruginosa Serogroup O2 Strains

Immunochemical and biochemical analysis of the polyvalent Pseudomonas aeruginosa vaccine PEV

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