Quantitative Determination in Human Sera of Vaccine-Induced Antibody to Type-Specific Polysaccharides of Group B Streptococci Using an Enzyme-Linked Immunosorbent Assay

Eisenstein, Toby K.; Cueninck, B J De; Resavy, D.; Shockman, Gérald D.; Carey, Roberta B.; Swenson, Robert M.

doi:10.1093/infdis/147.5.847

Cited by 55 publications

(15 citation statements)

References 21 publications

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“…We used linear regression of log-log-transformed data to calculate the slopes defined by diluting sera. In the III-HSA ELISA, the range of observed slopes for the test sera was 0.86 to 1.08, with the GBS III standards (SHRS III and reference serum 19) representing the median value (slopes of 0.95). There was no difference in the slopes of the titration curves for adult sera obtained before and after immunization (with unconjugated IIIPS or III-TT conjugate as the immunogen).…”

Section: Resultsmentioning

confidence: 99%

“…Quantitative precipitation has been employed by our group and by others to establish the concentration of polysaccharidespecific antibodies in reference sera used to standardize immunoassays (19,23,33). The concentration of IIIPS-specific antibody assigned to SHRS III, i.e., 88 g/ml, is based on the sum of the values obtained by quantitative precipitation of antibodies and by RABA for nonprecipitating antibodies (25).…”

Section: Discussionmentioning

confidence: 99%

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Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React withStreptococcus pneumoniaeType 14

et al. 2002

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Covalent linkage of a bacterial polysaccharide to a protein greatly enhances the carbohydrate's immunogenicity and its binding to solid surfaces in immunoassays. These findings have spurred the development of glycoconjugate vaccines to prevent serious bacterial infections as well as the use of glycoconjugates as coating antigens in bioassays. We evaluated sera from women immunized with unconjugated group B streptococcal (GBS) type III (GBS III) polysaccharide (IIIPS) or with IIIPS covalently linked to tetanus toxoid to assess specificity, sensitivity, and parallelism in dilution curves in two GBS III enzyme-linked immunosorbent assays (ELISAs). One assay used IIIPS mixed with methylated human serum albumin (IIIPS ؉ mHSA) as the coating antigen, and the other used IIIPS covalently linked to HSA (III-HSA). Each coating antigen was associated with a highly specific GBS III bioassay. The sensitivity was higher in the III-HSA ELISA, in which conjugated IIIPS is bound to the plates. Parallelism in titration curves was observed in the III-HSA but not in the IIIPS ؉ mHSA ELISA. The excellent correlation between the concentrations of GBS IIIPS-specific immunoglobulin G (IgG) and the opsonophagocytic activity of these antibodies indicated that the III-HSA assay can predict functionality of vaccine-induced IgG against GBS III disease. The structure of the repeating unit of the capsular polysaccharide of GBS III differs from that of Streptococcus pneumoniae type 14 (Pn14 PS) only by the presence on GBS III of a sialic acid residue at the end of the side chain. The majority of healthy adults responding to GBS III vaccines with a fourfold or greater increase in GBS III-specific IgG antibodies developed antibodies cross-reacting with Pn14 PS (i.e., desialylated GBS IIIPS). The proportion of GBS vaccine responders who developed IgG to the desialylated IIIPS did not depend on whether IIIPS was given in the unconjugated or conjugated form. When present, these vaccine-induced cross-reacting antibodies conferred in vitro antibodymediated opsonophagocytosis and killing of both GBS III and Pn14, two pathogens that cause invasive disease in young infants.Group B Streptococcus (GBS) is a leading cause of bacteremia, sepsis, pneumonia, and meningitis in neonates and infants less than 3 months of age (2, 3). Mothers of neonates developing serotype III GBS (GBS III) disease have low concentrations of antibodies to the type III capsular polysaccharide (IIIPS) in their sera at delivery (5). If sufficient amounts of maternal IIIPS-specific antibodies cross the placenta (9, 12), the neonate or young infant will be protected against invasive disease (4, 5). Naturally acquired IIIPS-specific antibodies are predominantly of the immunoglobulin G (IgG) isotype (9, 25), the only isotype passively and actively transported across the placenta to the neonate (30,34,36,41).The direct correlation between infant immunity to GBS III disease and the presence of maternal IIIPS-specific antibodies was first established with a radioactive-antigen binding assa...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React withStreptococcus pneumoniaeType 14

et al. 2002

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“…The reference sera were: tetanus immunoglobulin, containing 390 units/ml; GBS III CPS antiserum (standard serum 43) kindly provided by Dr T. Eisenstein, Philadelphia, USA, containing 416.9 ~tg ab/ml measured by precipitin reaction [12]. The IgG and IgM titre of this serum was 1 : 24,300 and 1 : 800 respectively (mean of 6 tests).…”

Section: Serological Methodsmentioning

confidence: 99%

“…Several investigations showed that the prevalence rates of serum antibodies to GBS III in healthy adults are relatively low [1,10,13,15]. There are conflicting results concerning the predominance of IgG or IgM of these antibodies in serum [1,10,12] and scarce information about the IgG subclass composition of naturally acquired antibodies. Placental transfer of all four IgG subclasses was reported to be free, but antibodies of the IgG1 subclass seem to pass the placenta better than those of the IgG2 subclass and at an earlier stage of pregnancy [11,20,21].…”

Section: Introductionmentioning

confidence: 99%

Isotype composition of antibodies to streptococcus group B type III polysaccharide and to tetanus toxoid in maternal, cord blood sera and in breast milk

et al. 1992

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Neonates are protected against group B streptococcal (GBS) infections and tetanus by transplacentally transferred serum antibodies. Antibodies of the immunoglobulin (Ig) G, IgM and IgA classes and IgG subclasses to the capsular polysaccharide (CPS) of type III group B streptococci (GBS III) and to tetanus toxoid (TT) were measured in sera from healthy women of fertile age and in paired maternal and cord blood sera from term and preterm pregnancies. GBS III CPS antibodies of the IgG class were found in sera from 97 out of 100 women of fertile age, but only 15 of them had antibodies above the proposed protective level (greater than or equal to 2 micrograms/ml). TT IgG antibodies above the protective level (0.01 units/ml) were found in all sera. The IgG antibodies against GBS III CPS were mainly composed of the IgG2 subclass and to a lesser extent of IgG1. Almost all women had IgG1 antibodies against TT and 40% had IgG4 antibodies. Total IgG and IgG1 antibodies against GBS III CPS were higher in cord blood sera from 37 term neonates than in sera from their mothers whereas IgG2 antibody levels were similar. Total IgG and IgG1 antibodies against TT were also higher in the 20 term neonates tested than in their mothers. In contrast, total IgG and IgG1 to both GBS III CPS and TT and IgG2 to GBS III CPS were lower in cord blood sera from preterm neonates than in sera from their mothers. IgA antibodies to GBS III CPS were detected in 63% of breast milk samples while IgA antibodies against TT were detected in only 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…As IgG class antibodies cross the placenta and could achieve protective levels in the fetus before delivery, immunization of women before or during pregnancy has been proposed as a strategy to prevent neonatal GBS infection (9,10). Purified preparations ofthree of the four major capsular polysaccharides (la, II, III) have been given as experimental vaccines both to animals and to human volunteers (9)(10)(11)(12)(13). While maternal vaccination appears to be a promising approach for preventing neonatal GBS disease, the native type III polysaccharide vaccine elicits a specific antibody response in only 60% of nonimmune recipients (10,12,13).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus.

Wessels¹,

Paoletti²,

Kasper³

et al. 1990

J. Clin. Invest.

187

171

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The native capsular polysaccharide of type III group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human sub-

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Quantitative Determination in Human Sera of Vaccine-Induced Antibody to Type-Specific Polysaccharides of Group B Streptococci Using an Enzyme-Linked Immunosorbent Assay

Cited by 55 publications

References 21 publications

Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React withStreptococcus pneumoniaeType 14

Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React withStreptococcus pneumoniaeType 14

Isotype composition of antibodies to streptococcus group B type III polysaccharide and to tetanus toxoid in maternal, cord blood sera and in breast milk

Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus.

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