Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B Streptococcus.

Baker, Carol J.; Kasper, Dennis L.; Tager, Ira B.; Paredes, Abel; Alpert, Susan; McCormack, William M.; Goroff, Diana K.

doi:10.1172/jci108703

Cited by 122 publications

(69 citation statements)

References 28 publications

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“…Since susceptibility to invasive infection in mice (4) and in human infants (6,23,24) correlates with low levels of serum antibody directed against the type-specific antigens of GBS, one proposed method for the prevention of neonatal disease is active immunization of child-bearing age women with these polysaccharides. This method presumes immunogenicity and safety of candidate vaccines, induction of IgG class antibody to insure placental transport, and protection by these maternally derived antibodies in neonates susceptible to invasive infection.…”

Section: Discussionmentioning

confidence: 99%

“…This method presumes immunogenicity and safety of candidate vaccines, induction of IgG class antibody to insure placental transport, and protection by these maternally derived antibodies in neonates susceptible to invasive infection. For type III GBS the first two requirements have been experimentally verified (24,25), although protective efficacy remains to be documented. Although little is known about human immunity to other serotypes of GBS, careful immunologic and chemical characterization of their surface antigens has served as a major approach to vaccine development.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies to the type Ia and III polysaccharides in sera from human volunteers were quantified by a radioactive antigen-binding assay (RABA) (23,24 Quantitative precipitin and quantitative precipitin inhibition studies were conducted as previously described (22 (25,26) were tested for the development of antibodies cross-reactive with the native type II polysaccharide. Sera were stored at -70°C before testing.…”

Section: Introductionmentioning

confidence: 99%

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Immunochemical analysis and immunogenicity of the type II group B streptococcal capsular polysaccharide.

Kasper¹,

Baker²,

Galdes³

et al. 1983

J. Clin. Invest.

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A B S T R A C T The relationship between group B streptococcal (GBS) type-specific antisera and the type II-specific polysaccharide is evaluated from a structural and immunologic viewpoint. Although all GBS type-specific polysaccharides are composed of the same monosaccharides, the type II antigen is more complex structurally and contains these sugars in a molar ratio different from the other antigens. Type II polysaccharide has two side chains. One contains only sialic acid and is less susceptible to acid cleavage than sialic acid residues found on types III, Ia, and Ib polysaccharides. The other side chain is composed of galactose as the only sugar. Immunochemical studies demonstrate that the type II polysaccharide has several immunodeterminants. One of these determinants is likely to be the side-chain galactose, while sialic acid appears to comprise part of another immunodeterminant, more complex than sialic acid alone. A series of cross-reactions is demonstrated between the type II native antigen and antisera to serotypes Ia, III, and Ib by a sensitive radioactive antigen-binding assay, which account for additional, complex immunodeterminants. The strongest of these cross-reactions is with type Ia antiserum and the weakest with lb antiserum. Since Ia and lb polysaccharides differ in only one linkage, these findings suggest that the trisaccharide BD-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunochemical analysis and immunogenicity of the type II group B streptococcal capsular polysaccharide.

Kasper¹,

Baker²,

Galdes³

et al. 1983

J. Clin. Invest.

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“…he concentration of antibody to native type Ia or 111 GBS polysaccharides in adult or neonatal human sera and in GPS was determined by a radioactive antigen-binding assay described previously (8,9). Antigens used in the present studies were purified native type 111 and type I11 capsular polysaccharides intrinsically labeled with I3H].…”

Section: Isolation Of Pmnmentioning

confidence: 99%

Impaired Chemotaxigenesis by Type III Group B Streptococci in Neonatal Sera: Relationship to Diminished Concentration of Specific Anticapsular Antibody and Abnormalities of Serum Complement

et al. 1983

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Summarynates and other individuals with disorders characterized bv a high A chemotaxigenesis (CTG) assay employing adult or neonatal sera, type I11 group B streptococci (GBS) and polymorphonuclear leukocytes (PMNs) was designed to evaluate the role of PMN mobilization in the pathogenesis of type 111 GBS infection in neonates. Generation of C5a in healthy adult sera with moderatehigh (3-40 pg/ml) or low (52 pg/ml) levels of specific anticapsular antibody was confirmed by PMN aggregometry and by the neutralization of CTG by goat anti-human C5. CTG was significantly ( P < 0.001) greater in high as compared to low specific antibodycontaining adult sera; stepwise increases in CTG occurred when specific IgG was added to untreated, but not heat-inactivated, hypogammaglobulinemic serum. Immunospecificity of CTG was shown by a failure of type 111 GBS to generate C5a in heterologous (type Ia) high antibody sera. Mean CTG values in three high and 16 low antibody-containing sera from healthy term neonates were 24% and 62% of high ( P < 0.001) and low (P < 0.01) antibody adult sera, respectively. The addition of both complement and specific IgG to low antibody-containing neonatal sera was required to enhance their CTG activity to high antibody adult values. CTG by type I11 GBS in neonatal sera-neonatal PMN mixtures was only 25% (high antibody sera) and 14% (low antibody sera) of values for paired maternal sera mixtures reacted with adult PMNs ( P < 0.001). These studies demonstrate that CTG by type I11 GBS in neonatal sera is markedly diminished and that low concentrations of specific anticapsular antibody and abnormalities of complement function contribute to impaired PMN mobilization in human neonates. AbbreviationsAb, antibody ACP, alternative complement pathway C4D, C4 deficiency CH50, hemolytic complement activity CL, chemoluminescence CTG, chemotaxigenesis DPBS, Dulbecco's Phosphate Buffered Saline GBS, group B streptococci GPS, guinea pig sera PMN, polymorphonuclear leukocyte THB, Todd-Hewett broth ZAP, zymosan-activated plasma Among inflammatory functions, the localized recruitment of phagocytic cells to foci of microbial invasion represents a critical and first line host defense mechanism (5, 32, 49). Impaired leukocyte tissue mobilization has been demonstrated in human neo-, U risk for the development of severe pyogenic infections (5,19,37). Previous investigations in human neonates have demonstrated abnormalities in both the humoral and cellular contributions to leukocyte motility in vitro (5,22,25,27,3 1,33,36,46), but specific serum requirements for generation of chemotactic factors (chemotaxigenesis) by GBS have not been determined. The experiments described in this report were designed to study the chemotactic properties of type 111 GBS and to define chemotaxigenic requirements in human sera for this serotype. Methods were developed to evaluate selectively the functional importance of serum antibody (IgG) specific for native 111 capsular polysaccharide and complement in the generation of C5a by GBS in sera fro...

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“…Therefore, susceptibility to invasive GBS disease may not be related just to the level of antibody in serum, but also to the characteristics of the invading GBS. Using a radioimmunoassay to measure antibody to GBS, Baker et al (6) found mothers of infants with type 111 disease to have a lower median antibody level as compared to antibody levels in mothers with healthy infants. However, there were wide ranges in antibody concentrations in each group.…”

Section: M891mentioning

confidence: 99%

Type III Group B Streptococcal Strain Differences in Susceptibility to Opsonization with Human Serum

1981

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SummaryHuman serum opsonins to type 111 Group B streptococci (GBS) were studied in an in vim opsonophagocytic assay. Two type 111 GBS test strains were susceptible (893 and IIINor) and two resistant (891 and 892) to opsonization by the majority of sera from 15 healthy adults. Four individuals with undetectable or low opsonic titers to the test strains were immunized with pneumococcal vaccine; immunization with pneumococcal vaccine induced a titer rise in all but one instance when susceptible GBS strains were tested. In contrast, only a single titer rise was detected when resistant GBS strains were employed in the test. These results indicate that immunization with a cross-reacting antigen (identical to core antigen of type 111 GBS) fails to induce opsonic antibody to all strains of type 111 GBS. A resistant strain was made highIy susceptible to neutrophil killing in vim by exposure to neuramindase prior to incubation with opsonic serum. Using a fluorescent lectin-biding assay, this enzyme appeared to remove surface sialic acid, suggesting that sialic acid is an antiphagocytic factor. However, the possibility that other surface moieties may act as antiphagocytic factors cannot be ruled out. Both opsonic suscep tible and resistant strains absorbed opsonic antibody from serum, which suggests that the GBS antiphagocytic factors do not prevent binding of antibody to resistant bacteria.These findings indicate that demonstration of serum opsonic activity to one strain of type I11 GBS may not accurately depict opsonic activity to other strains. In addition, immunization with core antigen did not enhance opsonic activity against all GBS strains. These data also point out the need to use assays which measure functional antibody, since demonstration of antibody binding may not reflect its ability to facilitate bacterial phagocytosis and killing.have demonstrated that passive administration of opsonic antibody may decrease mortality in neonatal GBS sepsis. It is important to note that survival correlated with the presence of opsonic antibody to the infecting GBS strain.In previous studies we have reported that type I11 GBS and ) have shown that individuals immunized with pneumococcal vaccine had weaker and less sustained GBS antibody responses than those individuals immunized with GBS antigen containing sialic acid. They also did not detect rises in opsonic antibody to type I11 GBS in those individuals immunized with pneumococcal vaccine who had lower pre-immunization levels of antibody to type 111 GBS. The present study further suggests that pneumococcal vaccine would not be an effective method of immunizing women against GBS. In the present study we identify type I11 GBS resistant to opsonization with human serum containing either naturally occurring or immunization-induced antibodies. Resistant bacteria were susce~ti-ble to opsonization after treatment with neuraminidase suggesting that sialic acid may function as an antiphagocytic factor in GBS resistant to opsonization. MATERIALS AND METHODSOver the last decade Strept...

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Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B Streptococcus.

Cited by 122 publications

References 28 publications

Immunochemical analysis and immunogenicity of the type II group B streptococcal capsular polysaccharide.

Immunochemical analysis and immunogenicity of the type II group B streptococcal capsular polysaccharide.

Impaired Chemotaxigenesis by Type III Group B Streptococci in Neonatal Sera: Relationship to Diminished Concentration of Specific Anticapsular Antibody and Abnormalities of Serum Complement

Type III Group B Streptococcal Strain Differences in Susceptibility to Opsonization with Human Serum

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