scholarly journals Immunization with C5a Peptidase or Peptidase-Type III Polysaccharide Conjugate Vaccines Enhances Clearance of Group B Streptococci from Lungs of Infected Mice

2002 ◽  
Vol 70 (11) ◽  
pp. 6409-6415 ◽  
Author(s):  
Qi Cheng ◽  
Steven Debol ◽  
Hong Lam ◽  
Ron Eby ◽  
Lorri Edwards ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Surface Protein ◽  
Histological Evaluation ◽  
Group B Streptococci ◽  
Type Iii ◽  
Rapid Clearance ◽  
Group B ◽  
The Impact

ABSTRACT Group B streptococci (GBS) are among the most common causes of life-threatening neonatal infections. Vaccine development since the late 1970s has focused on the capsular polysaccharides, but a safe, effective product is still not available. Our quest for a vaccine turned to the streptococcal C5a peptidase (SCPB). This surface protein is antigenically conserved across most if not all serotypes. A murine model was used to assess the impact of SCPB on clearance of GBS from the lungs of intranasally infected animals. Mutational inactivation of SCPB resulted in more-rapid clearance of streptococci from the lung. Immunization with recombinant SCPB alone or SCPB conjugated to type III capsular polysaccharide produced serotype-independent protection, which was evidenced by more-rapid clearance of the serotype VI strain from the lungs. Immunization of mice with tetanus toxoid-type III polysaccharide conjugate did not produce protection, confirming that protection induced by SCPB conjugates was independent of type III polysaccharide antigen. Histological evaluation of lungs from infected mice revealed that pathology in animals immunized with SCPB or SCPB conjugates was significantly less than that in animals immunized with a tetanus toxoid-polysaccharide conjugate. These experiments suggest that inclusion of C5a peptidase in a vaccine will both add another level to and broaden the spectrum of the protection of a polysaccharide vaccine.

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 Antibody against Surface-Bound C5a Peptidase Is Opsonic and Initiates Macrophage Killing of Group B Streptococci

2001 ◽  
Vol 69 (4) ◽  
pp. 2302-2308 ◽  
Author(s):  
Qi Cheng ◽  
Brian Carlson ◽  
Sub Pillai ◽  
Ron Eby ◽  
Lorri Edwards ◽  
...  
Keyword(s):  
Whole Blood ◽  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Primary Cultures ◽  
Surface Protein ◽  
Mouse Bone Marrow ◽  
Group B Streptococci ◽  
Protective Antibodies ◽  
Group B

ABSTRACT The capsular polysaccharides of group B streptococci (GBS) are a primary focus of vaccine development. Immunogenicity and long-lasting protection are best achieved by conjugating polysaccharides to a T-cell-dependent protein antigen. Streptococcal C5a peptidase (SCPB) is a conserved surface protein that is expressed by all streptococcal serotypes tested to date, and it is a possible carrier protein that could itself induce a protective immune response. Clearance of GBS from lungs, mucosal surfaces, or blood probably depends on the opsonophagocytic response of tissue-specific macrophages and polymorphonuclear leukocytes (PMNs). In this study, we examined the potential of antibody directed against SCPB from a serotype II strain to enhance the capacity of mouse bone marrow macrophages (from primary cultures) and human PMNs in whole blood to kill GBS in vitro. Our experiments demonstrated that Streptococcus serotypes Ia, Ib, II, III, and V, preopsonized with anti-SCPB antibody, were killed more rapidly by cultured macrophages and PMNs in whole blood than were nonopsonized GBS. The increased rate of killing was accompanied by an increased macrophage oxidative burst. Furthermore, opsonization was serotype transparent. Immunization with SCPB conjugated to capsular polysaccharide type III produced polysaccharide-specific antibodies. It is interesting that this antiserum promoted serotype-independent killing of streptococci. These data support the use of SCPB in a GBS polysaccharide conjugate vaccine. SCPB not only enhanced the immunogenicity of polysaccharide components of the vaccine, but it might also induce additional serotype-independent protective antibodies.

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

Specificity and Protective Activity of Murine Monoclonal Antibodies Directed Against the Capsular Polysaccharide of Type III Group B Streptococci

Hybridoma ◽  
1992 ◽  
Vol 11 (1) ◽  
pp. 13-22 ◽  
Author(s):  
G. TETI ◽  
M. CALAPAI ◽  
G. CALOGERO ◽  
F. TOMASELLO ◽  
G. MANCUSO ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Capsular Polysaccharide ◽  
Protective Activity ◽  
Group B Streptococci ◽  
Type Iii ◽  
Group B ◽  
Murine Monoclonal Antibodies

scholarly journals Molecular epidemiology of infections caused by group B Streptococcus in pregnant women and newborns, and development of preventive vaccines

2018 ◽  
Vol 67 (5) ◽  
pp. 62-73
Author(s):  
Vasilisa A. Vasilyeva ◽  
Elena V. Shipitsyna ◽  
Kira V. Shalepo ◽  
Alevtina M. Savicheva
Keyword(s):  
Capsular Polysaccharide ◽  
Vaccine Development ◽  
Current Knowledge ◽  
Group B Streptococcus ◽  
Epidemiological Data ◽  
Group B Streptococci ◽  
Group B ◽  
Sequence Types ◽  
Experimental Immunization ◽  
Selection Of

Hypothesis/aims of study. The present analysis was undertaken to summarize current knowledge about molecular properties of group B streptococci (GBS), emphasizing potential targets of vaccines against neonatal GBS infection. Study design, materials, and methods. This review is based on articles published mainly in the last ten years. Results. Epidemiological data on serotypes, multilocus sequence types, clonal complexes of GBS and their relationship are presented. Genetic events in GBS populations indicate significant obstacles to vaccine development. We described key properties of major GBS virulence factors, such as capsular polysaccharide, pili, and cell adhesion molecules, as well as results of experimental immunization on their basis. Conclusion. The population of invasive GBS strains is molecularly and genetically heterogeneous, which complicates selection of vaccine targets. Capsular switching, a low level of immunogenicity and variability of population composition are the most important factors that necessitate the accumulation and monitoring of molecular epidemiological data.

scholarly journals A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III

2018 ◽  
Vol 68 (12) ◽  
pp. 2079-2086 ◽  
Author(s):  
Sharon L Hillier ◽  
Patricia Ferrieri ◽  
Morven S Edwards ◽  
Marian Ewell ◽  
Daron Ferris ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Group B Streptococcus ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type Iii ◽  
Maternal Immunization ◽  
Young Infants ◽  
Group B

Abstract Background Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods Healthy, nonpregnant women aged 18–40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%–58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration NCT00128219.

scholarly journals Lectin Site Interaction with Capsular Polysaccharide Mediates Nonimmune Phagocytosis of Type III Group B Streptococci

2000 ◽  
Vol 68 (10) ◽  
pp. 5794-5802 ◽  
Author(s):  
E. A. Albanyan ◽  
M. S. Edwards
Keyword(s):  
Capsular Polysaccharide ◽  
Group B Streptococci ◽  
Type Iii ◽  
Group B

scholarly journals Nonopsonic Binding of Type III Group B Streptococci to Human Neutrophils Induces Interleukin-8 Release Mediated by the p38 Mitogen-Activated Protein Kinase Pathway

2000 ◽  
Vol 68 (4) ◽  
pp. 2053-2060 ◽  
Author(s):  
Esam A. Albanyan ◽  
Jesus G. Vallejo ◽  
C. Wayne Smith ◽  
Morven S. Edwards
Keyword(s):  
Capsular Polysaccharide ◽  
Kinase Inhibitor ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Human Neutrophils ◽  
Complement Receptor ◽  
Group B Streptococci ◽  
Type Iii ◽  
Mitogen Activated Protein ◽  
Group B

ABSTRACT Nonopsonic interaction of host immune cells with pathogens is an important first line of defense. We hypothesized that nonopsonic recognition between type III group B streptococcus and human neutrophils would occur and that the interaction would be sufficient to trigger neutrophil activation. By using a serum-free system, it was found that heat-killed type III group B streptococci bound to neutrophils in a rapid, stable, and inoculum-dependent manner that did not result in ingestion. Transposon-derived type III strain COH1-13, which lacks capsular polysaccharide, and strain COH1-11 with capsular polysaccharide lacking terminal sialic acid demonstrated increased neutrophil binding, suggesting that capsular polysaccharide masks an underlying binding site. Experiments using monoclonal antibodies to complement receptor 1 and to the I domain or lectin site of complement receptor 3 did not inhibit binding, indicating that the complement receptors used for ingestion of opsonized group B streptococci were not required for nonopsonic binding. Nonopsonic binding resulted in rapid activation of cellular p38 and p44/42 mitogen-activated protein kinases. This interaction was not an effective trigger for superoxide production but did promote release of the proinflammatory cytokine interleukin-8. The release of interleukin-8 was markedly suppressed by the p38 mitogen-activated protein kinase inhibitor SB203580 but was only minimally suppressed by the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059. Thus, nonopsonic binding of type III group B streptococci to neutrophils is sufficient to initiate intracellular signaling pathways and could serve as an arm of innate immunity of particular importance to the immature host.

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