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Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1110-1114, Vol. 8, No. 6
Department of Medical Microbiology, Faculty
of Medicine, University of Zimbabwe, Medical School, Avondale,
Harare, Zimbabwe,1 and Department of
Microbiology, School of Medicine, Norwegian University of Science
and Technology, N-7006 Trondheim, Norway2
Received 5 March 2001/Returned for modification 13 June
2001/Accepted 17 August 2001
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 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 Human sera.
A total of 100 sera from pregnant women in the
Trondheim area of Norway and 124 sera from pregnant women in the
Chinhoyi area of western Zimbabwe were examined. Sera were collected
during checkup visits to physicians or maternity clinics by women
between the fourth and eighth month of pregnancy and were handed to us blinded after routine testing in hospital laboratories. Only sera which
tested negative for hepatitis B surface antigen and human immunodeficiency virus were included in the study. The women ranged in
age from 17 to 38 years. For five Norwegian women giving birth at full
term, sera from both the mothers and the babies were collected and
analyzed. Sera were kept at
1071-412X/01/$04.00+0 DOI: 10.1128/CDLI.8.6.1110-1114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Antibodies against Streptococcus
agalactiae Proteins c
and R4 in Sera from
Pregnant Women from Norway and Zimbabwe
ABSTRACT
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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.
INTRODUCTION
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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). For this reason the
proteins or protein fragments have been considered vaccine candidates
(17). In this context the c and
R4 proteins should be of particular interest, since some 75% of GBS
isolates harbor one or the other of these proteins (19).
On this basis we figured that maternal antibodies against ladder-forming proteins could be one of the host factors which determine the outcome in newborns colonized by GBS, as has been suggested by others (25). For this reason we have measured
the levels of serum antibodies against c and
R4, the most prevalent of the laddering GBS proteins, in two groups of
pregnant women, one from Norway and one from Zimbabwe.
MATERIALS AND METHODS
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
20°C until tested.
Bacterial strains and culture.
GBS strains NCTC 12906 (strain 335; seroytpe Ia/c) and 65604 (serotype III/R4), our prototype strains for the
c and R4 proteins, respectively, were used for
the preparation of the c and R4 proteins. The
bacteria were cultured in Todd-Hewitt broth (10),
harvested by centrifugation (10,000 × g; 15 min), and washed with phosphate-buffered saline (PBS), pH 7.2.
Antigen preparation. The bacteria were extracted with trypsin (1 mg/ml) in 50 mM Tris buffer (pH 8.0); there was 5 ml of the solution per g of wet bacterial pellet.
The suspension was incubated at 37°C for 4 h and centrifuged (10,000 × g; 15 min). Proteins in the supernatant were precipitated with 5% (wt/vol) trichloroacetic acid (TCA) at 4°C for 20 h. The precipitate, which was collected by centrifugation, was dissolved in PBS and dialyzed against PBS, and proteins were precipitated with ammonium sulfate (pH 7.0; 72% saturation) at 4°C for 20 h. The final precipitate, collected by centrifugation, was dissolved in a small volume of PBS and applied to a Sephacryl S-200 HR (Pharmacia) column (60 by 1.6 cm). The column was equilibrated and eluted with PBS at an elution rate of 3 ml/h. Fractions of 1.6 ml were collected and were used in a dilution of 1:10 for coating microtiter plates to detect the presence of the c or R4 antigen by probing
with the appropriate antisera. The fractions, which contained the
c or R4 protein, were pooled and kept at
20°C in small aliquots. The fractions were also tested using the
Streptex kit (Murex Biotech. Ltd., Dartford, England).
Antisera.
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. In addition, rabbit antisera against whole
cells of GBS strains ATCC 12400 (090) and NCTC 11079, reference strains
for capsular antigen types Ia and II, respectively, were used.
Immunological techniques.
Immunoblotting was performed as
described previously (28). Briefly, fractions positive for
the c or R4 protein were subjected to sodium
dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to
polyvinylidene difluoride membranes (Bio-Rad, Richmond, Calif.), and
probed against PAbs (1:500) or MAbs (1:500). Antibody binding was
detected using the appropriate peroxidase-conjugated
anti-immunoglobulin preparation (1:1,000).
and R4 preparations was
tested by checkerboard titration using the appropriate PAbs (1:500),
MAbs (1:500), and gamma globulin preparation (1:2,000). The ELISA was
performed as described previously (28). Briefly, coating
(50 µl/well) was performed at 4°C for 20 h. Incubation with
human serum, antiserum, or alkaline phosphatase-conjugated antibodies
to immunoglobulins (1:1,000; Sigma) of the appropriate species
proceeded at 20°C for 1 h. Incubation with substrate
(p-nitrophenyl phosphate) was at 37°C for 30 min and was
followed by reading the signaling at 405 nm. Negative controls included
testing without antigen and testing without human or animal antibodies.
Washings were performed using PBS with 0.05% (vol/vol) Tween 20 (PBST), which also served as the diluent. All tests were performed in duplicate. Background signaling was recorded but was not subtracted from the recordings obtained with the various sera. The results are
presented as ELISA ratio obtained by dividing the mean of the optical
density at 405 nm (OD405) signaled by the human
serum when tested in a dilution of 1:200 by that recorded with gamma globulin when tested in a dilution of 1:2,000.
Inhibition ELISA was performed by mixing equal volumes of the antigen
solution tested for inhibition or PBST (positive control) and
appropriately diluted gamma globulin, MAbs, or PAbs and by incubating
the mixture at 20°C for 1 h. The mixture was then tested as in the indirect ELISA. The gamma globulin and antisera were used in
dilutions which resulted in OD405 recordings for
the positive controls in the range of 1.000 to 1.200. Inhibition was
expressed as percentage reduction of the signaling caused by the
competing antigen from the signaling shown by the positive control,
tested on the same microtiter plate.
Statistical methods. The Mann-Whitney U test was used for comparison of differences between population groups. The Stat-Med statistical program was used for linear regression and Pearson's correlation calculations. Values of P <0.05 were considered statistically significant.
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RESULTS |
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Abstract
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Materials and Methods
Results
Discussion
References
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The c and R4 antigens.
GBS strains 335 (Ia/c) and 65604 (III/R4) were digested by
trypsin, and extracted material was isolated by TCA precipitation and
then by ammonium sulfate precipitation. The c
or R4 proteins which were contained in the precipitate were further purified by sieve chromatography. Both proteins were eluted from the
Sephacryl S-200 HR column as sharp and symmetrical peaks corresponding to the void volume of the column. Fractions close to the total volume
of the column contained UV light-absorbing material, but coats prepared
with this material showed no MAb or PAb binding activity. The pooled
void volume fractions gave rise to ladder-like patterns in Western
blotting, as previously described for c
(7) and R4 (8); the patterns seemed identical
when probed with the anti-whole-cell PAbs and MAbs, respectively. The
material showed no reactivity when tested by the Streptex kit, and
coats prepared with it were negative when tested by ELISA with
rabbit antibodies used to detect capsular antigens Ia and III,
respectively, in a fluorescent antibody test (5, 9). For
both of the protein antigens, a dilution of 1:10 was optimal for
coating in an ELISA to detect human or animal antiprotein antibodies.
In the ELISA, the anti-c MAb and PAbs
recognized only c and the corresponding
anti-R4 antibodies recognized only the R4 protein. Antisera against
whole cells of our reference strains for capsular antigens Ia and II
(which do not express the c and/or the R4
protein), both of which were sera with high levels of antibodies
against the homologous strain, showed no antibody activity against
c and R4 when dilutions from 1:100 were tested.
Levels of anti-c and anti-R4 antibodies in sera from
pregnant women.
Figure 1 shows the
titration curves for c- and R4-reactive
antibodies in a commercial human gamma globulin preparation. An increase or decrease in the ELISA ratio of 0.200 to 0.300 corresponded to approximately a doubling or halving, respectively, of the antibody concentration. Repeated testing of the gamma globulin (1:2,000) showed
OD405 readings (means ± standard
deviations) of 0.906 ± 0.234 against
c and 0.984 ± 0.249 against R4 with
background signaling values of 0.112 ± 0.049 and 0.096 ± 0.030, respectively, similar to the background signaling recorded with
a 1: 200 dilution of individual human sera.
|
-GL)
preparation tested in ELISA against the GBS c
) and the R4 protein (
). OD405 readings at the
1:2,000 dilution were the basis for estimation of the ELISA ratio.
and anti-R4 antibody levels were
significantly higher in the Norwegian population than in the Zimbabwean
population. On the basis of an arbitrary selection of ELISA ratios of
>0.250 as an indication of the presence of these antibodies, 91% of
the Norwegian sera and 69% of the Zimbabwean sera contained
anti-c IgG antibodies and 92 and 73% of the
sera, respectively, contained anti-R4 antibodies.
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Specificity of antibodies.
It was observed that individual
sera showed the same or nearly the same ELISA ratios for the
anti-c and anti-R4 antibodies, as if the two
antigens measured the same antibody. This accordance was evaluated for
the first 20 sera tested in each of the two population groups examined.
For both the Norwegian sera (Fig. 3) and
the Zimbabwean sera, the correlation between the
c and R4 ELISA ratios was highly significant
(r = 0.977 and 0.915, respectively; P<
0.01), supporting the suspicion that the human serum antibodies
recognized a target(s) which was common to the c and R4 proteins. This supposition was
substantiated by the finding that c and R4
neutralized the R4-reactive human serum antibodies to the same extent
(84 and 82% inhibition for the c and R4
proteins, respectively) but not the vaccination-induced R4-reactive
rabbit antibodies (1 and 100% inhibition for the
c and R4 proteins, respectively).
Analogous results were obtained in the inhibition ELISA when the
c protein was used for coating and human or
immune anti-c antibodies were used for
probing, i.e., both c and R4 neutralized the
c-reactive human antibodies but only
c neutralized the
anti-c antibodies raised in animals (data not
shown).
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DISCUSSION |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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In this study we measured the levels of serum IgG antibodies
against GBS proteins c and R4 in groups of
pregnant women from Norway and Zimbabwe. One of these proteins (rarely
both) is expressed by at least 75% of GBS strains (19).
Since both c and R4 are ladder-forming GBS
proteins and since these proteins are targets of protective antibodies
in experimental models (1, 17, 22, 24, 31), these antigens
have been considered vaccine candidates either alone or as the protein
component in a capsular polysaccharide-protein conjugate vaccine
(17). On this basis we hypothesized that the testing
described in the present study could be the measurement of serum
antibodies which are important in protection against GBS disease,
particularly neonatal disease.
After trypsin extraction and sequential precipitation with TCA and
ammonium sulfate and gel filtration, the proteins appeared immunologically homogenous, as evidenced by the failure to detect serogroup or capsular polysaccharides, by Western blotting findings, and by the results of testing with antisera raised against whole cells
of GBS strains which do not express the c or
R4 protein. We anticipated that trypsin, efficient for extraction of
these proteins (13), would cleave a variety of
contaminating GBS proteins and thereby would facilitate separation of
the contaminants from the high-molecular-weight
c and R4 proteins by the fractionation procedure.
We chose to match antibody levels in the population groups tested
against the levels in a human gamma globulin preparation, although it
has been established that different commercial gamma globulin
preparations vary considerably in GBS antibody levels, including
opsonic activity (14, 33), mostly depending on the donor pool (33). The latter observation is consistent with
our findings that the Norwegian group of pregnant women had
significantly higher levels of both c- and
R4-reactive antibodies than a corresponding group of Zimbabwean women.
This difference cannot be attributed to GBS carrier rate in pregnancy,
which was higher in a Zimbabwean (29) than in a Norwegian
(15) group of pregnant women. Genetic factors and/or factors related to socioeconomic standards and nutritional status may
account for this difference. The design of the study did not permit
adequate evaluation of the impact of such factors.
Although antibody levels varied up to manyfold between individuals, at
least 70% of the Zimbabwean women and 90% of the Norwegian women had
c- and R4-reactive antibodies. For
c this is considerably higher than the value
found previously by testing blood donors (6). However, the
results of the present study compare favorably with the results of
testing of anti-R4 antibodies by Western immunoblotting
(12). In that study 92.5% of colonized mothers and 54%
of noncolonized mothers had detectable levels of these antibodies. Some
investigators have noticed an increase in anti-GBS antibodies in
urogenital secretions, but less of an increase in serum
antibodies, in GBS carriers compared to noncarriers
(16). We did not discriminate between carriers and
noncarriers among the individuals tested but considered it likely that
the anti-c and -R4 antibodies detected in the
human sera were induced by GBS carriage.
We noticed that the c- and R4-reactive
antibodies showed identical or similar levels of signaling in ELISA for
both individual human sera and the gamma globulin preparation and that
this accordance was statistically significant. This prompted inhibition
experiments which showed that c and R4 were
equally effective as competing antigens for antibodies in the gamma
globulin preparation, irrespective of which of the two proteins was
used for coating, indicating a common c and R4
site targeted by the human antibodies. To our knowledge this is the
first presentation of such specificity of human antibodies recognizing
the c and R4 antigens. This was unlike what
was found for the antibodies induced in animals, which demonstrated
specificity for the homologous antigen. The c
protein, the most extensively characterized of the ladder-forming GBS
proteins, has epitopes in the repeats and in the N-terminal region,
both of which are targeted by protective antibodies (17). Our results support the notion that the natural human serum antibodies target c and R4 sites which are distinct from
the sites targeted by the immune antibodies induced in animals. In that
case, the functions of the human antibodies, such as
immunoprotection in neonates and adults, may differ from the protective
function established for antibodies raised in animals (17, 24,
31). This remains a challenge for future studies.
In conclusion, our data show that serum from the majority of adult
women from an African and a Scandinavian country contained serum
antibodies which recognized the GBS proteins c
and R4. These antibodies probably target sites different from the sites
targeted by immune antibodies raised in animals. The human
c- and R4-reactive antibodies require further
studies, including studies to clarify their immunobiological function.
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ACKNOWLEDGMENTS |
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We are grateful to Randi V. Lyng for her technical assistance and L. Bevanger for fruitful discussions.
This work was supported by grants from the University of Zimbabwe Research Board and the Norwegian Quota program for students from developing countries and central and eastern Europe.
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Microbiology, School of Medicine, Norwegian University of Science and Technology, N-7006 Trondheim, Norway. Phone: (47) 73868484. Fax: (47) 73867765. E-mail: Johan.Meland{at}medisin.ntnu.no.
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REFERENCES |
|---|
|
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Abstract
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Materials and Methods
Results
Discussion
References
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|---|
| 1. |
Areschoug, T.,
M. Stålhammar-Carlemalm,
C. Larsson, and G. Lindahl.
1999.
Group B streptococcal surface proteins as targets for protective antibodies: identification of two novel proteins in strains of serotype V.
Infect. Immun.
67:6350-6357 |
| 2. | Baker, C. F. 1997. Group B streptococcal infections. Clin. Perinatol. 24:59-70[Medline]. |
| 3. | Baker, C. F., and D. L. Kasper. 1976. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N. Engl. J. Med. 294:753-756[Abstract]. |
| 4. | Baker, C. F., B. F. Webb, D. L. Kasper, M. D. Yow, and C. W. Beachler. 1980. The natural history of group B streptococcal colonization in the pregnant woman and her offspring. II. Determination of serum antibody to capsular polysaccharide from type III group B streptococcus. Am. J. Obstet. Gynecol. 137:39-42[Medline]. |
| 5. | Bevanger, L. 1983. Ibc proteins as serotype markers of group B streptococci. Acta Pathol. Microbiol. Immunol. Scand. Sect. B 91:231-234[Medline]. |
| 6. |
Bevanger, L.
1985.
The Ibc proteins of group B streptococci: isolation of the  and  antigens by immunosorbent chromatography and test for human serum antibodies against the two antigens.
Acta Pathol. Microbiol. Immunol. Scand. Sect. B
93:113-119[Medline].
|
| 7. |
Bevanger, L.,
O.-J. Iversen, and A. I. Naess.
1992.
Characterization of the -antigen of the c proteins of group B streptococci (GBS) using a murine monoclonal antibody.
APMIS
100:57-62[Medline].
|
| 8. | Bevanger, L., A. I. Kvam, and J. A. Maeland. 1995. A Streptococcus agalactiae R protein analysed by polyclonal and monoclonal antibodies. APMIS 103:731-736[Medline]. |
| 9. | Bevanger, L., and J. A. Maeland. 1977. Type classification of group B streptococci by the fluorescent antibody test. Acta Pathol. Microbiol. Immunol. Scand Sect. B 85:357-362. |
| 10. | Bevanger, L., and J. A. Maeland. 1979. Complete and incomplete Ibc protein fraction in group B streptococci. Acta Pathol. Microbiol. Immunol. Scand. Sect. B 87:51-54. |
| 11. | Blumberg, H. M., D. S. Stephens, M. Modansky, M. Erwin, J. Elliot, R. R. Facklam, A. Schuchat, W. Baughman, and M. M. Farley. 1996. Invasive group B streptococcal disease: the emergence of serotype V. J. Infect. Dis. 173:365-373[Medline]. |
| 12. | Fasola, E. L., A. E. Flores, and P. Ferrieri. 1996. Immune responses to the R4 protein antigen of group B streptococci and its relationship to other streptococcal R4 proteins. Clin. Diagn. Lab. Immunol. 3:321-325[Abstract]. |
| 13. | Flores, A. E., and P. Ferrieri. 1996. Molecular diversity among the trypsin resistant surface proteins of group B streptococci. Zentbl. Bakteriol. 285:44-51. |
| 14. |
Givner, L. B.
1990.
Human immunoglobulins for intravenous use: comparison of available preparations for group B streptococcal antibody levels, opsonic activity, and efficacy in animal models.
Pediatrics
86:955-962 |
| 15. | Hordnes, K., M. Eide, M. Ulstein, A. Digranes, and B. Haneberg. 1995. Evaluation of a rapid enzyme immunoassay for detection of genital colonization of group B streptococci in pregnant women: own experience and review. Aust. N. Z. J. Obstet. Gynaecol. 35:251-253[Medline]. |
| 16. | Hordnes, K., T. Tynning, A. I. Kvam, L. Bevanger, T. A. Brown, R. Jonsson, and B. Haneberg. 1998. Cervical secretions in pregnant women colonized rectally with group B streptococci have high levels of antibodies to type III polysaccharide capsular antigen and protein R. Scand. J. Immunol. 47:179-188[CrossRef][Medline]. |
| 17. | Kling, D. E., C. Gravekamp, L. C. Madoff, and J. L. Michel. 1997. Characterization of two distinct opsonic and protective epitopes within the alpha C protein of the group B Streptococcus. Infect. Immun. 65:1462-1467[Abstract]. |
| 18. | Kvam, A. I., L. Bevanger, and J. A. Maeland. 1999. Properties and distribution of the putative R3 protein of Streptococcus agalactiae. APMIS 107:869-874[Medline]. |
| 19. |
Kvam, A. I.,
A. Efstratiou,
L. Bevanger,
B. D. Cookson,
I. F. Marticorena,
R. C. George, and J. A. Maeland.
1995.
Distribution of serovariants of group B streptococci in isolates from England and Norway.
J. Med. Microbiol.
42:246-250 |
| 20. |
Lachenauer, C. S.,
R. Creti,
J. L. Michel, and L. C. Madoff.
2000.
Mosaicism in the alpha-like protein genes of group B streptococci.
Proc. Natl. Acad. Sci. USA
97:9630-9635 |
| 21. | Lachenauer, C. S., D. L. Kasper, J. Shimada, Y. Ichiman, H. Ohtsuka, M. Kaku, L. C. Paoletti, P. Ferrieri, and L. C. Madoff. 1999. Serotypes VI and VIII predominate among group B streptococci isolated from pregnant Japanese women. J. Infect. Dis. 179:1030-1033[CrossRef][Medline]. |
| 22. | Lachenauer, C. S., and L. C. Madoff. 1996. A protective surface protein from type V group B streptococci shares N-terminal sequence homology with the alpha C protein. Infect. Immun. 64:4255-4260[Abstract]. |
| 23. | Lancefield, R. C., and G. E. Perlmann. 1952. Preparation and properties of a protein (R antigen) occurring in streptococci of group A, type 28 and in certain streptococci of other serological groups. J. Exp. Med. 96:83-97[Abstract]. |
| 24. |
Larsson, C.,
M. Stålhammar-Carlemalm, and G. Lindahl.
1996.
Experimental vaccination against group B streptococcus, an encapsulated bacterium, with highly purified preparations of cell surface proteins Rib and .
Infect. Immun.
64:3518-3523[Abstract].
|
| 25. | Linden, V., K. K. Christensen, and P. Christensen. 1983. Correlation between low levels of maternal IgG antibodies to R protein and neonatal septicemia with group B streptococci carrying R protein. Int. Arch. Allergy Appl. Immunol. 71:168-172[Medline]. |
| 26. | Madoff, C. L., and D. L. Kasper. 1993. Group B streptococcal disease, p. 210-224. In D. D. Charles (ed.), Obstetric and perinatal infection (handbook of infectious disease). Mosby Year Book, Inc., St. Louis, Mo. |
| 27. |
Michel, J. L.,
L. C. Madoff,
K. Olson,
D. E. Kling,
D. L. Kasper, and F. M. Ausubel.
1992.
Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci.
Proc. Natl. Acad. Sci. USA
89:10060-10064 |
| 28. | Moyo, S. R., J. A. Maeland, and L. Bevanger. 1999. Comparison of three different methods in monoclonal antibody-based detection of Streptococcus agalactiae protein serotype markers. APMIS 107:263-269[Medline]. |
| 29. | Moyo, S. R., J. Mudzori, S. A. Tswana, and J. A. Maeland. 2000. Prevalence, capsular type distribution, anthropometric and obstetric factors of group B streptococcus (Streptococcus agalactiae) colonization in pregnancy. Cent. Afr. J. Med. 46:115-120[Medline]. |
| 30. |
Schuchat, A.
1998.
Epidemiology of group B streptococcal disease in the United States: shifting paradigms.
Clin. Microbiol. Rev.
11:497-513 |
| 31. |
Stålhammar-Carlemalm, M.,
L. Stenberg, and G. Lindahl.
1993.
Protein Rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infection.
J. Exp. Med.
177:1593-1603 |
| 32. |
Wästfelt, M.,
M. Stålhammar-Carlemalm,
A.-M. Delisse,
T. Cabezon, and G. Lindahl.
1996.
Identification of a family of streptococcal surface proteins with extremely repetitive structures.
J. Biol. Chem.
271:18892-18897 |
| 33. | Weisman, L. E., D. F. Cruess, and G. W. Fisher. 1994. Opsonic activity of commercially available standard intravenous immunoglobulin preparations. Pediatr. Infect. Dis. J. 13:1122-1125[Medline]. |
Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1110-1114, Vol. 8, No. 6
1071-412X/01/$04.00+0 DOI: 10.1128/CDLI.8.6.1110-1114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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