Characterization of the a antigen of the c proteins of group B streptococci (GBS) using a murine monoclonal antibody

Bevanger, Lars; Iversen, Ole‐Jan; Naess, Augusta Irene

doi:10.1111/j.1699-0463.1992.tb00839.x

Cited by 21 publications

(40 citation statements)

References 11 publications

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“…Since alignments of sequences from the strain 515 whole-genome data and bca (C␣) sequences showed that the Alp1 and C␣ repeats were nearly identical, we tend to conclude that the Alp1/C␣ common site is located in the repeat region of the two Alps. Also the repeat region of the two protein antigens must be the targets for our anti-C␣ MAb which recognizes C␣ and Alp1 equally well (4,17). Over the years, this MAb has been used as a reagent in our laboratory to detect C␣, which has resulted in identification of Alp1-expressing isolates as C␣-expressing strains.…”

Section: Discussionmentioning

confidence: 99%

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Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

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Most isolates of group B streptococci (GBS) express an alpha-like protein (Alp), C␣ (encoded by bca), Alp1 (also called epsilon; alp1), Alp2 (alp2), Alp3 (alp3), Alp4 (alp4), or R4/Rib (rib). These proteins are chimeras with a mosaic structure and with antigenic determinants with variable immunological crossreactivities between the Alps, including Alp1 and C␣ cross-reactivity. This study focused on antigenic domains of Alp1, studied by using rabbit antisera in immunofluorescence, Western blotting, and enzymelinked immunosorbent assay (ELISA)-based tests and whole cells of GBS or trypsin-extracted and partially purified antigens from the strains A909 (serotype Ia/C␣, C␤) and 335 (Ia/Alp1). Alp1 and C␣ shared an antigenic determinant, Alp1/C␣ common, not harbored by other Alps, probably located in the Alp1 and C␣ repeat units, as these units are nearly identical in genomic sequence. An antigenic Alp1 determinant was Alp1 specific and was most likely located in the N-terminal unit of Alp1 in which an Alp1-specific primer site for PCR is also located. In addition, Alp1 possessed a domain with low immunogenicity which cross-reacted immunologically with Alp2 and Alp3, with unknown location in Alp1. Alp1 was partially degraded by trypsin during antigen extraction but with the antigenic domains preserved. The results indicate that C␣ and Alp1 are immunologically related in the same manner that R4 (Rib) and Alp3 are related. The domain called Alp1 specific should be important in GBS serotyping as a surface-anchored serosubtype marker. The Alp1/C␣ common determinant may be of prime interest as an immunogenic domain in a GBS vaccine.Group B streptococci (GBS) can be classified into 10 serotypes based on the capsular polysaccharides (CPS), serotypes Ia, Ib, and II through IX. In addition, a number of surfaceanchored and strain-variable protein antigens enable serosubtyping of GBS, resulting in a large number of GBS serovariants. For example, 25 different serovariants were identified in a GBS strain collection from Zimbabwe (19). The surfacelocalized proteins include C␤ encoded by bac, C␣ (bca), the alpha-like proteins (Alps) Alp1 (alp1; also called epsilon), Alp2 (alp2), Alp3 (alp3), Alp4 (alp4), R4/Rib (rib), the GBS protective protein R5 (sar5) (8), the R3 protein (11, 32), and a recently described novel protein called Z (20). Neither R3 nor Z has as yet been sequenced. The Alps are chimeras with a mosaic structure composed of an N terminus with 220 to 230 amino acids (aa), including the signal sequence (6), an area with a variable number of identical, tandem repeats, each containing ϳ80 aa, and a C terminus (12,15,22,31). The structural arrangement provides for protein-specific immune reactions in some cases and variable immunological crossreactivities between the proteins. Epitopes of the Alps induce antibodies which protect against GBS infection in experimental models, including cross-protection by cross-reacting antibodies (1,12,15,27,33).The C␣-encoding gene bca was the first Alp gene sequenced (GenBank accession no....

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Section: Discussionmentioning

confidence: 99%

“…Antisera. Rabbit antisera and a murine anti-C␣ monoclonal antibody (MAb) were both raised against whole cells of GBS as previously described (2,4). The rabbit antisera were used unabsorbed or after cross-absorption as specified in Results.…”

Section: Methodsmentioning

confidence: 99%

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Kvam

Mavenyengwa

Radtke

et al. 2011

Clin. Vaccine Immunol.

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“…Serotyping is based primarily on the GBS capsular polysaccharide antigens (CPA) designated Ia, Ib and II-VIII [4]. Sometimes, the CPA typing is supplemented by identification of serosubtype markers, strain-variable protein antigens such as c AE [5,6], c â [5], and the R proteins R1-R4 [7,8]. In addition, a number of other GBS protein antigens have been described, some of which showed cross-reactivity with classical R protein antigens.…”

Section: Introductionmentioning

confidence: 99%

Typing of human isolates of Streptococcus agalactiae (group B streptococcus, GBS) strains from Zimbabwe

Moyo¹,

Mæland

Bergh

2002

Journal of Medical Microbiology

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Serotyping and genotyping are important tools in epidemiological studies of group B streptococcal (GBS) infections, which are important diseases in man, particularly in newborns. In the present study, 241 GBS isolates from Zimbabwe, comprising 124 carrier isolates from pregnant women and 117 isolates from patients hospitalised for various diseases, were serotyped. Antibodies specific for the capsular polysaccharide antigens (CPAs) Ia, Ib and II-V and antibodies specific for the surface-localised proteins, c AE , c â , R1, R3 and R4 were used for serotyping. Strains of the CPA types Ia (17%), III (47.7%) and V (23.2%) predominated. Of the various protein antigens, c AE and R4 were expressed with highest frequency, c AE by 100% of the CPA type Ia strains and R4 by 92% of the CPA type III strains. The R3 protein occurred frequently (24%), especially in type V strains (84%). A total of 25 serovariants was detected in the strain collection with the variants Ia=c AE (16%), III=R4 (43.5%) and V=c AE , R3 (14.1%) occurring with the highest frequency. Serotype and subtype distribution of the carrier isolates were essentially similar to those of the disease-associated isolates. Genomic heterogeneity was demonstrated by pulsed-field gel electrophoresis of type III=R4 and type V=c AE , R3 isolates, but to a much lesser extent than recorded with Norwegian strains. These results demonstrate that many variants of GBS occur in the Zimbabwean population. The data obtained may assist in the formulation of a possible future GBS vaccine for Zimbabwe and perhaps for other African countries.

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“…Anti-c ␣ and anti-R4 monoclonal antibodies (MAbs) used in this study were those described previously (7,8). Polyclonal antibodies (PAbs) included antibodies raised in rabbits against whole cells of strains 335 and 65604, as described previously (8), and antisera raised against the purified c ␣ (7) and R4 (8) proteins.…”

Section: Methodsmentioning

confidence: 99%

“…These proteins include the c ␣ protein of the c protein fraction of GBS (7,10), the R1 to R4 proteins (8,13,18,23), protein Rib (31), a Rib-like protein (1), and c ␣ -like proteins (20,22). Large tandem repeats are additional characteristic features of these proteins (20,27,32), which harbor epitopes targeted by protective antibodies, according to experimental models (1,17,22,31).…”

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confidence: 99%

Antibodies against Streptococcus agalactiae Proteins c ^α and R4 in Sera from Pregnant Women from Norway and Zimbabwe

Moyo

Mæland

Mudzori

2001

Clin Diagn Lab Immunol

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Group B streptococci (GBS) express strain-variable and surface-localized proteins, which are important serotype markers and targets of protective antibodies. These include the c ␣ and R4 proteins, one or the other of which is expressed by approximately 75% of clinical GBS isolates. These proteins have been considered vaccine candidates. In this study, the c ␣ and R4 proteins were extracted by trypsin digestion of GBS and purified by sequential precipitation with trichloroacetic acid and ammonium sulfate followed by gel filtration chromatography. The proteins were used as antigens in an indirect enzyme-linked immunosorbent assay (ELISA) to measure the levels of c ␣ -and R4-reactive antibodies in sera from pregnant women from Norway (n ‫؍‬ 100) and from Zimbabwe (n ‫؍‬ 124). Antibody levels in the Norwegian group of women were significantly higher than in the Zimbabwean group, and a higher proportion of the Norwegian women contained appreciable levels of antibodies against both proteins. The antibodies traversed the placental barrier. With individual sera, a significant correlation between the anti-c ␣ and anti-R4 antibody levels was observed and each of the two protein antigens effectively competed for human serum antibodies both against itself and against the other antigen. Inhibition ELISA results demonstrated specificity for each of the proteins of immune antibodies raised in rabbits. These results demonstrate that (i) the majority of women of childbearing age have antibodies against c ␣ and R4, (ii) the levels of these antibodies differ among pregnant women in different parts of the world, and (iii) the normal human serum antibodies may target a common c ␣ and R4 protein site, whereas immune antibodies targeted a different site(s) specific for each protein.Group B streptococci (GBS) remain an important cause of morbidity and sometimes mortality in neonates and also a cause of maternal infections and infections in nonpregnant adults, in spite of antibiotic and supportive therapy (2, 30).Both host factors and microbial factors determine the outcome in infected individuals, including colonized newborns (30). The level of serum antibodies to capsular polysaccharide GBS antigens is one important host factor (3, 4). Up to now, nine different capsular antigen types have been defined. Among these, types Ia, Ib, II, and III predominate in many parts of the world (19, 26), but serotype V GBS has emerged as an increasingly important pathogen in some areas (11) and serotype VI and VIII strains are important pathogens in Japan (21).Many GBS strains also produce one or more proteins characterized by, among other things, resistance to trypsin digestion and formation of ladder-like banding patterns on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. These proteins include the c ␣ protein of the c protein fraction of GBS (7, 10), the R1 to R4 proteins (8, 13, 18, 23), protein Rib (31), a Rib-like protein (1), and c ␣ -like proteins (20,22). Large tandem repeats are additional characteristic feat...

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Characterization of the a antigen of the c proteins of group B streptococci (GBS) using a murine monoclonal antibody

Cited by 21 publications

References 11 publications

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Typing of human isolates of Streptococcus agalactiae (group B streptococcus, GBS) strains from Zimbabwe

Antibodies against Streptococcus agalactiae Proteins c ^α and R4 in Sera from Pregnant Women from Norway and Zimbabwe

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Characterization of the a antigen of the c proteins of group B streptococci (GBS) using a murine monoclonal antibody

Cited by 21 publications

References 11 publications

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Streptococcus agalactiae Alpha-Like Protein 1 Possesses Both Cross-Reacting and Alp1-Specific Epitopes

Typing of human isolates of Streptococcus agalactiae (group B streptococcus, GBS) strains from Zimbabwe

Antibodies against Streptococcus agalactiae Proteins c α and R4 in Sera from Pregnant Women from Norway and Zimbabwe

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Antibodies against Streptococcus agalactiae Proteins c ^α and R4 in Sera from Pregnant Women from Norway and Zimbabwe