scholarly journals Recombinant Group B Streptococcus Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein

2008 ◽  
Vol 15 (7) ◽  
pp. 1035-1041 ◽  
Author(s):  
Hsiao-Hui Yang ◽  
Samantha J. Mascuch ◽  
Lawrence C. Madoff ◽  
Lawrence C. Paoletti
Keyword(s):  
Capsular Polysaccharide ◽  
Human Peripheral Blood ◽  
Rabbit Serum ◽  
Specific Response ◽  
Carrier Protein ◽  
Blood Leukocytes ◽  
C Protein ◽  
Type Iii ◽  
Group B

ABSTRACT Conjugate vaccines against pathogens of multiple serotypes are optimized when all components induce functional antibody, resulting in broadened coverage. While most clinical studies of vaccines against group B Streptococcus (GBS) have evaluated conjugates composed of capsular polysaccharide (CPS) coupled to tetanus toxoid, conjugates prepared with GBS proteins as carriers have also been efficacious in animals. Here, we report that recombinant GBS alpha-like protein 3 (rAlp3) is both a strong immunogen and a viable carrier protein for type III CPS. The type III CPS-specific immunoglobulin G (IgG) titer rose from <100 to 64,000 among mice that received type III CPS coupled to rAlp3 (III-rAlp3) compared with an absence of a specific response among mice that received an uncoupled mixture. Most (94%) newborn pups born to III-rAlp-vaccinated dams survived challenge with viable type III GBS, compared with 43% survival among those born to dams that received the uncoupled mixture (P < 0.0001). A tricomponent conjugate of type III CPS, rAlp3, and a GBS recombinant beta C protein lacking its IgA binding site (III-rAlp3-rBCPΔIgA) provided protection against a serotype III strain and a serotype Ia strain bearing beta C protein. High-titered anti-rAlp3 rabbit serum opsonized Alp3-containing strains of two GBS serotypes (types V and VIII) and invasive type III strains bearing the cross-reactive Rib protein for in vitro killing by human peripheral blood leukocytes. Thus, the potential exists for the inclusion of rAlp3 in a GBS vaccine formulated to provide multiserotype coverage.

scholarly journals Alpha C Protein as a Carrier for Type III Capsular Polysaccharide and as a Protective Protein in Group B Streptococcal Vaccines

1999 ◽  
Vol 67 (5) ◽  
pp. 2491-2496 ◽  
Author(s):  
Claudia Gravekamp ◽  
Dennis L. Kasper ◽  
Lawrence C. Paoletti ◽  
Lawrence C. Madoff
Keyword(s):  
Conjugate Vaccine ◽  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Protein A ◽  
Surface Protein ◽  
Negative Control ◽  
Group B Streptococci ◽  
C Protein ◽  
Type Iii ◽  
Group B

ABSTRACT The alpha C protein, a protective surface protein of group B streptococci (GBS), is present in most non-type III GBS strains. Conjugate vaccines composed of the alpha C protein and type III capsular polysaccharide (CPS) might be protective against most GBS infections. In this study, the type III CPS was covalently coupled to full-length, nine-repeat alpha C protein (resulting in III-α9r conjugate vaccine) or to two-repeat alpha C protein (resulting in III-α2r conjugate vaccine) by reductive amination. Initial experiments with the III-α9r vaccine showed that it was poorly immunogenic in mice with respect to both vaccine antigens and was suboptimally efficacious in providing protection in mice against challenge with GBS. Therefore, modified vaccination protocols were used with the III-α2r vaccine. Female mice were immunized three times with 0.5, 5, or 20 μg of the III-α2r vaccine with an aluminum hydroxide adjuvant and bred. Ninety-five percent of neonatal mice born to dams immunized with the III-α2r vaccine survived challenge with GBS expressing type III CPS, and 60% survived challenge with GBS expressing wild-type (nine-repeat) alpha C protein; 18 and 17%, respectively, of mice in the negative control groups survived (P, <0.0001). These protection levels did not differ significantly from those obtained with the type III CPS-tetanus toxoid conjugate vaccine and the unconjugated two-repeat alpha C protein, which protected 98 and 58% of neonates from infection with GBS expressing type III CPS or the alpha C protein, respectively. Thus, the two-repeat alpha C protein in the vaccine was immunogenic and simultaneously enhanced the immunogenicity of type III CPS. III-α vaccines may be alternatives to GBS polysaccharide-tetanus toxoid vaccines, eliciting additional antibodies protective against GBS infection.

scholarly journals Type III Group B Streptococcal Polysaccharide Induces Antibodies That Cross-React with Streptococcus pneumoniae Type 14

2002 ◽  
Vol 70 (4) ◽  
pp. 1724-1738 ◽  
Author(s):  
Hilde-Kari Guttormsen ◽  
Carol J. Baker ◽  
Moon H. Nahm ◽  
Lawrence C. Paoletti ◽  
Susu M. Zughaier ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Sialic Acid Residue ◽  
Coating Antigen ◽  
Type Iii ◽  
Young Infants ◽  
Covalently Linked ◽  
Group B

ABSTRACT 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 antibody-mediated opsonophagocytosis and killing of both GBS III and Pn14, two pathogens that cause invasive disease in young infants.

Initial Studies of the Molecular Basis of Peptide Mimicry of Group B Streptococcal Type III Capsular Polysaccharide

2001 ◽  
Vol 20 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Seth H. Pincus ◽  
Stephen R. Lepage ◽  
Robert F. Jung ◽  
Jennifer G. Massey ◽  
Mahesh Jaseja
Keyword(s):  
Molecular Basis ◽  
Capsular Polysaccharide ◽  
Type Iii ◽  
Peptide Mimicry ◽  
Group B

Group B Streptococcal and Pneumococcal Sepsis in Newborn Infants: The Role of Pneumococcal Antibody

PEDIATRICS ◽  
1978 ◽  
Vol 62 (4) ◽  
pp. 620-621
Author(s):  
Gerald W. Fischer ◽  
James W. Bass ◽  
George H. Lowell ◽  
Martin H. Crumrine
Keyword(s):  
Streptococcus Pneumoniae ◽  
Hydrochloric Acid ◽  
Group B Streptococcus ◽  
Newborn Infants ◽  
Polysaccharide Antigen ◽  
Type Iii ◽  
Pneumococcal Sepsis ◽  
Group B

The article by Bortolussi et al. on pneumococcal septicemia and meningitis in the neonat (Pediatrics 60:352, September 1977) was of great interest to us, since we have been analyzing the effect of antibody directed against Streptococcus pneumoniae on group B Streptococcus type III. We have recently shown (unpublished data) that antibody directed against S. pneumoniae type 14 precipitates the hot hydrochloric acid-extracted polysaccharide antigen of group B Streptococcus type III. Further studies have shown that this antibody is opsonic for group B Streptococcus type III in an in vitro bactericidal assay and protective in a suckling rat model of group B Streptococcus type III sepsis.1

scholarly journals Capsular polysaccharide regulates neutrophil complement receptor interactions with type III group B streptococci.

1993 ◽  
Vol 61 (7) ◽  
pp. 2866-2871 ◽  
Author(s):  
M S Edwards ◽  
M R Wessels ◽  
C J Baker
Keyword(s):  
Capsular Polysaccharide ◽  
Complement Receptor ◽  
Group B Streptococci ◽  
Type Iii ◽  
Receptor Interactions ◽  
Group B

scholarly journals Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

2017 ◽  
Vol 51 (2) ◽  
pp. 39-45
Author(s):  
Milena Jankovic ◽  
Lada Zivkovic ◽  
Andrea Pirkovic ◽  
Dijana Topalovic ◽  
Dragana Dekanski ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Salvianolic Acid B ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Salvianolic Acid

scholarly journals Immune reactions in human filariasis

1978 ◽  
Vol 8 (2) ◽  
pp. 228-232 ◽  
Author(s):  
D Subrahmanyam ◽  
K Mehta ◽  
D S Nelson ◽  
Y V Rao ◽  
C K Rao
Keyword(s):  
Immunoglobulin G ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Wuchereria Bancrofti ◽  
Normal Subjects ◽  
Peripheral Blood Leukocytes ◽  
51Cr Release ◽  
Blood Leukocytes ◽  
Release Studies

Sera from cases of elephantiasis due to Wuchereria bancrofti infection promoted an intense adhesion of peripheral blood leukocytes to W. bancrofti microfilariae in vitro. A similar adhesion was also seen using sera from some normal persons living for several years in areas where filariasis is endemic. No such adhesion was evident with sera from microfilaria carriers or from normal subjects from nonendemic areas. The adhesion was complement independent and was associated with the immunoglobulin G fraction of serum. 51Cr release studies suggested the occurrence of cell-mediated cytotoxicity to W. bancrofti microfilariae in the presence of elephantiasis serum. Microfilariae of Litomosoides carinii could be isolated free of blood cells, from the blood of infected rats. In the presence of serum, or its immunoglobulin G fraction, from patients with elephantiasis, L. carinii microfilariae adhered to human peripheral blood leukocytes or rat spleen cells.

scholarly journals Differential Infectivity and Division ofToxoplasma gondii in Human Peripheral Blood Leukocytes

2000 ◽  
Vol 68 (8) ◽  
pp. 4822-4826 ◽  
Author(s):  
Jacqueline Y. Channon ◽  
Rosanne M. Seguin ◽  
Lloyd H. Kasper
Keyword(s):  
Dendritic Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Differential Infectivity

ABSTRACT When tachyzoites were incubated with human peripheral blood leukocytes in vitro, more monocytes and dendritic cells than neutrophils or lymphocytes were infected. Although tachyzoites were able to divide in each of these cell types, monocytes and dendritic cells were more permissive to rapid tachyzoite division than neutrophils or lymphocytes.

Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fields

2005 ◽  
Vol 26 (4) ◽  
pp. 258-265 ◽  
Author(s):  
O. Zeni ◽  
M. Romanò ◽  
A. Perrotta ◽  
M.B. Lioi ◽  
R. Barbieri ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Leukocytes ◽  
Genotoxic Effects ◽  
Blood Leukocytes ◽  
In Vitro Exposure
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