scholarly journals OC 8465 THE DEVELOPMENT OF A CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS: AN AFRICAN PERSPECTIVE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A8.1-A8
Author(s):  
Seanette Wilson ◽  
Patrick Tippoo
Keyword(s):  
South Africa ◽  
Clinical Trial ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Disease Risk ◽  
Group B Streptococcus ◽  
International Health ◽  
Infant Deaths ◽  
Young Infants ◽  
Group B

BackgroundStreptococcus agalactiae, or group B streptococcus (GBS), is a gram-positive streptococcal bacterium that is well-recognised as one of the leading causes of infant death, particularly in the early neonatal period (the first week of life). An estimated one in five pregnant women around the world carries GBS bacteria in their gastrointestinal or genitourinary tracts and vertical transmission from colonised mothers can lead to invasive disease in their offspring. A recent study conservatively estimated that out of 410,000 GBS cases globally every year, there are at least 1 47 000 stillbirths and infant deaths. Despite being home to only 13% of the world’s population, Africa has the highest GBS disease burden, with 54% of estimated cases and 65% of stillbirths and infant deaths.An effective GBS vaccine, given during pregnancy, is a promising strategy to protect against GBS disease. Currently, no licensed vaccine exists to prevent it, but scientific evaluation of feasibility is favourable. The leading vaccine candidates are capsular polysaccharide-protein conjugate vaccines. Evidence suggests maternal immunisation with a safe and effective GBS vaccine may reduce the disease risk in neonates and young infants.The Biovac Institute was established as a private-public partnership and is the only Southern African vaccine manufacturer. Located in Cape Town, South Africa, Biovac’s mission is to become a leading vaccine developer and producer in South Africa to increase capacity in Africa which only has four other vaccine manufacturers.In collaboration with PATH, an international health organisation, and other partners, Biovac is developing a multivalent conjugate vaccine against GBS. The first stage of the project involves the development of biopharmaceutical manufacturing processes and analytical tests, the preparation of clinical trial product, and execution of a first-in-human clinical trial.This presentation will provide an overview of the project, progress to date, and the path to commercialisation.

scholarly journals Estimation of invasive Group B Streptococcus disease risk in young infants from case-control serological studies

2021 ◽  
Author(s):  
Alane Izu ◽  
Gaurav Kwatra ◽  
Shabir A Madhi ◽  
Fabio Rigat
Keyword(s):  
Disease Risk ◽  
Group B Streptococcus ◽  
Case Control ◽  
Antibody Concentration ◽  
Case Control Studies ◽  
Clinical Interpretation ◽  
Young Infants ◽  
Risk Estimates ◽  
Group B ◽  
Non Parametric

Abstract Background: Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable use of efficient clinical trial designs for vaccine development and licensure, without needing to undertake efficacy trials in prohibitively large number of mother-infant dyads. The association of maternal naturally acquired serotype-specific anti-capsular antibodies (IgG) against serotype-specific IGbsD in their infants has been studied in case-control studies. The statistical models used so far to estimate IGbsD risk from these case-control studies assumed that the antibody concentrations measured sharing the same disease status are sampled from the same population, not allowing for differences between mothers colonised by GBS and mothers also potentially infected (e.g urinary tract infection or chorioamnionitis) by GBS during pregnancy. This distinction is relevant as infants born from infected mothers with occult medical illness may be exposed to GBS prior to the mother developing antibodies measured in maternal or infant sera. Methods: Unsupervised mixture model averaging (MMA) is proposed and applied here to accurately estimate infant IGbsD risk from case-control study data in presence or absence of antibody concentration subgroups potentially associated to maternal GBS carriage or infection. MMA estimators are compared to non-parametric disease risk estimators in simulation studies and by analysis of two published GBS case-control studies. Results: MMA provides more accurate relative risk estimates under a broad range of data simulation scenarios and more accurate absolute disease risk estimates when the proportion of IGbsD cases with high antibody levels is not ignorable. MMA estimates of the relative and absolute disease risk curves are more amenable to clinical interpretation compared to non-parametric estimates with no detectable overfitting of the data. Antibody concentration thresholds predictive of protection from infant IGbsD estimated by MMA from maternal and infant sera are consistent with non-parametric estimates. Conclusions: MMA is a flexible and robust method for design, accurate analysis and clinical interpretation of case-control studies estimating relative and absolute IGbsD risk from antibody concentrations measured at or after birth.

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 Structure‐Guided Design of a Group B Streptococcus Type III Synthetic Glycan–Conjugate Vaccine

2020 ◽  
Vol 26 (31) ◽  
pp. 6944-6944 ◽  
Author(s):  
Davide Oldrini ◽  
Linda Bino ◽  
Ana Arda ◽  
Filippo Carboni ◽  
Pedro Henriques ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Group B Streptococcus ◽  
Type Iii ◽  
Group B

Synthesis of a disialylated hexasaccharide of Type VIII Group B Streptococcus capsular polysaccharide

1999 ◽  
Vol 319 (1-4) ◽  
pp. 1-16 ◽  
Author(s):  
Eva Eichler ◽  
Harold J. Jennings ◽  
Michel Gilbert ◽  
Dennis M. Whitfield
Keyword(s):  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Type Viii ◽  
Group B

Serological and conformational properties of E. coli K92 capsular polysaccharide and its N-propionylated derivative both illustrate that induced antibody does not recognize extended epitopes of polysialic acid: Implications for a comprehensive conjugate vaccine against groups B and C N. meningitidis

2002 ◽  
Vol 80 (8) ◽  
pp. 1055-1063 ◽  
Author(s):  
Robert A Pon ◽  
Nam Huan Khieu ◽  
Qing-Ling Yang ◽  
Jean-Robert Brisson ◽  
Harold J Jennings
Keyword(s):  
Molecular Dynamics ◽  
Immune Response ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Competitive Inhibition ◽  
Polysialic Acid ◽  
E Coli ◽  
Protective Epitope ◽  
Conformational Properties ◽  
Group B

The capsular polysaccharide of E. coli K92 (K92P) contains elements in common with the capsular polysaccharides of both groups B and C N. meningitidis, and may therefore form the basis of a bivalent vaccine. In an attempt to augment the cross-protective immune response to group B meningococci, the N-acetyl groups of the K92P were replaced by N-propionyl groups (NPrK92P) and conjugated to protein. This strategy had previously been applied with success to the poorly immunogenic capsular polysaccharide of group B meningococcus (GBMP), and the bactericidal epitope was found to be exclusively mimicked by extended helical segments of the NPrGBMP. The NPrK92P-conjugate, in relation to a K92P-conjugate, failed to enhance the response to GBMP but did generate a measurable response to NPrGBMP, but only at the expense of a greatly reduced GCMP response. Despite the presence of an immune response to NPrGBMP, the anti-NPrK92 serum was not bactericidal. Competitive inhibition studies with NPrGBMP oligosaccharides suggested the NPrK92 antibodies could not cross-react with the protective epitope on group B meningococci, as defined by extended helical segments of the NPrGBMP, but only recognized short non-bactericidal NPrGBMP epitopes. This hypothesis was supported from the conformational and molecular dynamics studies of the K92P, which demonstrated a lack of extended conformations that resemble the GBMP extended epitope. Indeed, the conformational properties of the K92P more closely resembled those of the GCMP, thereby explaining the observed moderate cross-protection of the K92P antiserum towards group C meningococci. Thus, on the basis of these results, it can be concluded that K92P, regardless of N-propionyl modification, will not serve as an effective single vaccine component against both groups B and C meningococci.Key words: conjugate vaccine, Neisseria meningitidis, polysialic acid, NMR, molecular dynamics.

Sign in / Sign up

Export Citation Format

Share Document