Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A

Fattom, Ali; Schneerson, Rachel; Watson, Douglas C.; Karakawa, Walter W.; FitzGerald, David J.; Pastan, Ira; Li, Xiuru; Shiloach, Joseph; Bryla, Dolores A.; Robbins, John B.

doi:10.1128/iai.61.3.1023-1032.1993

Cited by 120 publications

(32 citation statements)

References 52 publications

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“…Capsular serotyping of the coded isolates (no patient identifiers were used) was performed by direct cell agglutination and immunoprecipitation of cell extracts as described previously (21). Two different types of rabbit serum samples were used to identify the capsular type of each isolate: sera from animals vaccinated with a whole-cell vaccine (21) and monospecific sera against either type 5 or type 8 capsular polysaccharide conjugated vaccine prepared in rabbits (11,12). Monoclonal antibodies to capsular types 5 and 8 produced and standardized by NABI (Rockville, Md.)…”

Section: Study Design and Data Collection A Total Of 785 Patients Admentioning

confidence: 99%

Phenotypic and Genotypic Characterization of Nosocomial Staphylococcus aureus Isolates from Trauma Patients

Nawas

Hawwari²,

Hendrix

et al. 1998

J Clin Microbiol

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Staphylococcus aureus is a major cause of nosocomial infections. During the period from March 1992 to March 1994, the patients admitted to the intensive care unit of the University of Maryland Shock Trauma Center were monitored for the development ofS. aureus infections. Among the 776 patients eligible for the study, 60 (7.7%) patients developed 65 incidents of nosocomialS. aureus infections. Of the clinical isolates, 43.1% possessed a polysaccharide type 5 capsule, 44.6% possessed a type 8 capsule, and the remaining 12.3% had capsules that were not typed by the type 5 or type 8 antibodies. Six antibiogram types were noted among the infection-related isolates, with the majority of the types being resistant only to penicillin and ampicillin. It was noted that the majority of cases of pneumonia were caused by relatively susceptible strains, while resistant strains were isolated from patients with bacteremia and other infections. Only 16 (6.3%) of the isolates were found to be methicillin-resistant S. aureus (MRSA). DNA fingerprinting by pulsed-field gel electrophoresis showed 36 different patterns, with characteristic patterns being found for MRSA strains and the strains with different capsular types. Clonal relationships were established, and the origins of the infection-related isolates in each patient were determined. We conclude that (i) nosocomial infection-related isolates from the shock trauma patients did not belong to a single clone, although the predominance of a methicillin-resistant genotype was noted, (ii) most infection-relatedS. aureus isolates were relatively susceptible to antibiotics, but a MRSA strain was endemic, and (iii) for practical purposes, the combination of the results of capsular and antibiogram typing can be used as a useful epidemiological marker.

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Section: Study Design and Data Collection A Total Of 785 Patients Admentioning

confidence: 99%

Phenotypic and Genotypic Characterization of Nosocomial Staphylococcus aureus Isolates from Trauma Patients

Nawas

Hawwari²,

Hendrix

et al. 1998

J Clin Microbiol

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“…In the experiments reported here, two proteins of medical interest with lower molecular weights than TT, the B subunit of the heat-labile cholera-like enterotoxin (LT-B) of Escherichia coli and the recombinant exoprotein A (rEPA) of Pseudomonas aeruginosa, were used as carriers for Vi (7,8,14,15). The immunogenicity of these conjugates in young mice and guinea pigs and their safety in adult volunteers are described.…”

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confidence: 99%

Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines

et al. 1994

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To improve its immunogenicity for children and adults and to make it suitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B subunit of the heat-labile toxin (LT-B) of Escherichia coli or the recombinant exoprotein A (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of serum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elicited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA, respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 versus 1.77; P < 0.005) and 26 weeks later (2.32 and 2.69 versus 0.54; P < 0.04); a second injection of the conjugates did not elicit a booster response of Vi antibodies. None of the 51 vaccinees had fever or significant local reactions. Vi-rEPA elicited slightly higher levels of Vi antibodies than did Vi-LT-B at all intervals after injection, but these differences were not significant. Each conjugate elicited antibodies to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharide-protein conjugates. These conjugates promise to be an improved Vi vaccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned. Typhoid fever remains a common and serious disease in many parts of the world (11, 33). Treatment of typhoid fever has become more difficult with the emergence of antibioticresistant strains of Salmonella typhi (2, 4, 43). The development of a capsular polysaccharide (Vi) of S. typhi provided a simple

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“…In the mouse model, antibodies elicited by the S. aureus bivalent T5/ 8 conjugate vaccine are said to be functional and a high degree of correlation has been reported to exist between antibody titer by ELISA and opsonic activity by in vitro opsonophagocytosis. 8 The T5 and T8 PS-specific antibodies from both vaccinated humans and animals have been shown to induce type-specific opsonophagocytic killing of S. aureus, 29,30 and are protective in both lethality and sublethality mouse models. 31 Thus serum IgG responses to T5/ 8 PS by ELISA have been used as surrogate markers for the protectiveness of this vaccine.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

Bolgiano²,

Martino³

et al. 2006

Human Vaccines

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A bivalent, unadjuvanted conjugate vaccine composed of Staphylococcus aureus capsular polysaccharides type 5 and 8 (T5 and T8 PS) conjugated to a novel carrier protein, the mutant nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has been the subject of recent clinical trials. A program of preclinical laboratory evaluation was carried out in support of the clinical trials conducted by the National Vaccine Evaluation Consortium. This involved physical chemical characterization and limited assessment of toxicity and immunogenicity. The carrier protein showed good stability and its conformation was essentially maintained when conjugated. The T5- and T8-rEPA conjugates were of a size range (1-3 x 10(6) g/ mol) consistent with polysaccharide conjugates. Fluorescence spectroscopy and molecular sizing showed good batch-to-batch consistency. Although all batches of final fill preparations elicited positive immune responses in the mouse model with three schedule doses of 0.25 microg of each T5/8 conjugate per dose, the mouse serum IgG response to T8 PS varied from batch to batch. Storage temperature at 37 degrees C or below or with repetitive temperature fluctuations did not significantly affect the IgG responses to T5 or T8 PS. Storage at 56 degrees C, however, diminished the mouse serum IgG response to T5 PS. The conformation of the conjugated protein and size of the conjugates correlated well with mouse immunogenicity in the thermal stability samples; significant unfolding of the protein and downshifts in molecular size of the conjugate were only observed when stored at 56 degrees C. The relatively high stability of the novel carrier protein when conjugated to large polysaccharides makes this an attractive candidate carrier protein for other conjugate vaccines. When assayed for serum IgG concentration, the bivalent T5/ 8 conjugate was found to evoke an IgG response well over the threshold value of 10 microg/ ml anti-T5 and -T8 IgG established for the ELISA immunogenicity assay.

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Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A

Cited by 120 publications

References 52 publications

Phenotypic and Genotypic Characterization of Nosocomial Staphylococcus aureus Isolates from Trauma Patients

Phenotypic and Genotypic Characterization of Nosocomial Staphylococcus aureus Isolates from Trauma Patients

Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines

Preclinical Laboratory Evaluation of a BivalentStaphylococcus aureusSaccharide: Exotoxin A Protein Conjugate Vaccine

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