Capsular Polysaccharide Of Streptococcus Research Articles

Association between anti-capsular IgG levels at birth and risk of invasive group B streptococcus disease in Finnish newborns: a retrospective case–control study

Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants. In this retrospective case-control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia-V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk-concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data. Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120-0·266 μg/mL serotype III-specific IgG was estimated to confer 75-90% risk reduction against serotype III disease. A universal risk-concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease. Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious. Pfizer.

Interlaboratory comparison of a multiplex immunoassay that measures human serum IgG antibodies against six-group B streptococcus polysaccharides

ABSTRACT Measurement of IgG antibodies against group B streptococcus (GBS) capsular polysaccharide (CPS) by use of a standardized and internationally accepted multiplex immunoassay is important for the evaluation of candidate maternal GBS vaccines in order to compare results across studies. A standardized assay is also required if serocorrelates of protection against invasive GBS disease are to be established in infant sera for the six predominant GBS serotypes since it would permit the comparison of results across the six serotypes. We undertook an interlaboratory study across five laboratories that used standardized assay reagents and protocols with a panel of 44 human sera to measure IgG antibodies against GBS CPS serotypes Ia, Ib, II, III, IV, and V. The within-laboratory intermediate precision, which included factors like the lot of coated beads, laboratory analyst, and day, was generally below 20% relative standard deviation (RSD) for all six serotypes, across all five laboratories. The cross-laboratory reproducibility was < 25% RSD for all six serotypes, which demonstrated the consistency of results across the different laboratories. Additionally, anti-CPS IgG concentrations for the 44-member human serum panel were established. The results of this study showed assay robustness and that the resultant anti-CPS IgG concentrations were reproducible across laboratories for the six GBS CPS serotypes when the standardized assay was used.

Immune responses against group B Streptococcus monovalent and pentavalent capsular polysaccharide tetanus toxoid conjugate vaccines in Balb/c mice

Immunization of pregnant women with Group B Streptococcus (GBS) capsular polysaccharide (CPS) conjugate vaccine (CV) could protect young infants against invasive GBS disease. We evaluated the immunogenicity of investigational five GBS monovalent (serotypes Ia, Ib, II, III, and V) CPS-tetanus toxoid (TT)-CV with adjuvant and GBS pentavalent CPS-TT-CV with adjuvant (GBS5-CV-adj) and without adjuvant (GBS5-CV-no-adj), in Balb/c mice. Aluminum phosphate was the adjuvant in the formulations, where included. The homotypic immunoglobulin G (IgG) geometric mean concentration (GMC) and opsonophagocytic activity (OPA) geometric mean titer (GMT) did not differ after the third dose of the GBS5-CV-adj vaccine compared with the monovalent counterparts for all five serotypes. The GBS5-CV-adj induced higher post-vaccination serotype-specific IgG GMCs and OPA GMTs compared to GBS5-CV-no_adj. The GBS5-CV with and without adjuvant should be considered for further development as a potential vaccine for pregnant women to protect their infants against invasive GBS disease.

Stereodirecting Effects of 4‐O‐ortho‐cyanobenzyl Ether on Chemical Glycosylation with Glucopyranosyl Donor

Comprehensive SummaryHere we report a systematic investigation on the stereodirecting effects of a 4‐O‐ortho‐cyanobenzyl ether (oBCN) group with a glucopyranosyl donor. Experimental studies revealed that the glycosylation reactions using this donor generally show dual‐stereoselectivities depending on the acceptor nucleophilicity, that is, glycosylation of weak nucleophile acceptors generally affords α‐glycosides specifically while glycosylation of strong nucleophile acceptors affords β‐glycosides preferentially. DFT computations suggested that strong nucleophiles preferentially attack the predominant covalent α‐glycosyl triflate intermediate in an SN2‐like manner, while weak nucleophiles preferentially attack the less stable and more reactive β‐glycosyl triflate with H‐bond mediated direction. The first and facile synthesis of a hexasaccharide repeating unit of serotype IV group B Streptococcus capsular polysaccharide demonstrated the versatile utility of glucosyl building blocks with an oBCN functionality in carbohydrate chemistry.

Serum immunoglobulins and anti-pneumococcal antibody levels in patients with bronchiectasis of unknown aetiology

Background: Bronchiectasis is a chronic condition which can result in significant physical and social morbidity. The exact prevalence in Malaysia is unknown although several studies have shown a higher prevalence in the Asian population. Several causative factors have been identified but there are many patients with unknown aetiologies. This study looks into the level of serum immunoglobulins and antipenumococcal antibody in bronchiectasis patients where they were not part of prior routine investigations.&#x0D; Methodology: Four hundred fifteen bronchiectasis patients were screened and 26 patients who fulfilled the inclusion and exclusion criteria were enrolled for this study. The serum immunoglobulins (IgG, IgA and IgM) concentrations were measured using nephelometry and interpreted according to age-matched reference range. The integrity of antibody production against specific antibody to capsular polysaccharides of Streptococcus pneumoniae were assessed using ELISA method and the level of ≥ 10mg/L is considered as reactive.&#x0D; Results: The twenty six bronchiectasis patients have the mean age of 62 years and a predilection of female gender. Majority of patients presented with typical bronchiectasis symptoms which were further supported by radiological findings. One of 26 patients (4%) had low total serum IgG level. The vaccinated group has higher anti-pneumococcal capsular polysaccharide antibody level (median: 224.2 mg/L) compared to the unvaccinated group (median: 100.4 mg/L). However there is no statistical difference between the anti-PCP levels of both groups (p&gt; 0.05). All of the selected patients had reactive specific antibody to capsular polysaccharides of Streptococcus pneumoniae regardless of the vaccination status, which may reflect the natural acquisition of anti-pneumococcal immunity.&#x0D; Conclusion: Although immunoglobulin deficiency is an uncommon aetiological cause of bronchiectasis, the immunoglobulin parameters can be helpful in selecting patients who should receive the appropriate treatment of immunoglobulin therapy for the prevention of subsequent complications and better quality of life.&#x0D; Bangladesh Journal of Medical Science Vol.19(2) 2020 p.200-207

Group A, B, C, and G Streptococcus Lancefield antigen biosynthesis is initiated by a conserved α-d-GlcNAc-β-1,4-l-rhamnosyltransferase

Group A carbohydrate (GAC) is a bacterial peptidoglycan-anchored surface rhamnose polysaccharide (RhaPS) that is essential for growth of Streptococcus pyogenes and contributes to its ability to infect the human host. In this study, using molecular and synthetic biology approaches, biochemistry, radiolabeling techniques, and NMR and MS analyses, we examined the role of GacB, encoded in the S. pyogenes GAC gene cluster, in the GAC biosynthesis pathway. We demonstrate that GacB is the first characterized α-d-GlcNAc-β-1,4-l-rhamnosyltransferase that synthesizes the committed step in the biosynthesis of the GAC virulence determinant. Importantly, the substitution of S. pyogenes gacB with the homologous gene from Streptococcus agalactiae (Group B Streptococcus), Streptococcus equi subsp. zooepidemicus (Group C Streptococcus), Streptococcus dysgalactiae subsp. equisimilis (Group G Streptococcus), or Streptococcus mutans complemented the GAC biosynthesis pathway. These results, combined with those from extensive in silico studies, reveal a common phylogenetic origin of the genes required for this priming step in >40 pathogenic species of the Streptococcus genus, including members from the Lancefield Groups B, C, D, E, G, and H. Importantly, this priming step appears to be unique to streptococcal ABC transporter–dependent RhaPS biosynthesis, whereas the Wzx/Wzy-dependent streptococcal capsular polysaccharide pathways instead require an α-d-Glc-β-1,4-l-rhamnosyltransferase. The insights into the RhaPS priming step obtained here open the door to targeting the early steps of the group carbohydrate biosynthesis pathways in species of the Streptococcus genus of high clinical and veterinary importance.

One-Pot Synthesis of the Repeating Unit of Type VII Group B Streptococcus Polysaccharide and the Dimer.

The first synthesis of the hexasaccharide repeating unit of type VII group B Streptococcus capsular polysaccharide was achieved by a one-pot glycosylation strategy. The dimer of this repeating unit was also synthesized by one-pot glycosylation to achieve the backbone hexasaccharide first followed by one-pot dual glycosylations with the side-chain trisaccharide donor. All glycosylation reactions gave excellent stereoselectivity, which took advantage of a new stereospecific α-glucosylation method and the neighboring group participation effect for 1,2- trans glycosylations.

Chemical synthesis of the dimeric repeating unit of type Ia group B Streptococcus capsular polysaccharide.

The first chemical synthesis of the dimeric repeating unit of serotype Ia group B Streptococcus capsular polysaccharide was achieved. The on-site elongation and dual glycosylation strategies were utilized to construct two sialotrisaccharide branches based on a hexasaccharide containing adjacent 3,4-di-branched Gal units, which were synthesized via a preactivation-based one-pot glycosylation method.

Chemical Synthesis of the Repeating Unit of Type II Group B Streptococcus Capsular Polysaccharide.

The first chemical synthesis of the repeating unit of serotype II group B Streptococcus capsular polysaccharide, a branched heptasaccharide α-Neu p5Ac-(2→3)-β-d-Gal p-(1→4)-β-d-GlcN pAc-(1→3)-{[β-d-Gal p-(1→6)]-β-d-Gal p}-(1→4)-β-d-Glc p-(1→3)-β-d-Glc p-(1→, was achieved by convergent [4+2+1] glycosylation, after probing different synthetic strategies and overcoming a series of difficulties. The title compound was designed to carry a free amino group at its downstream end to enable further regioselective elaboration. This work also revealed that the α-Neu5Ac-(2→3)-β-d-Gal-(1→4)-β-d-GlcNAc motif, which is common in natural glycans, had a low reactivity as glycosyl donors, so it was rather difficult to directly couple this trisaccharide with sterically hindered acceptors. The motif was efficiently constructed via on-site glycan elongation using properly protected GlcN and α-Neu5Ac-(2→3)-β-d-Gal as consecutive glycosyl donors.

Nuclear magnetic resonance assessment of controlled hydrolysis of the capsular polysaccharides of Streptococcus pneumoniae serotypes 19A and 19F

ABSTRACTSeveral glycoconjugate-based vaccines are inserted nowadays in infant vaccination schedules of most countries. In an initial stage, polysaccharides are modified under controlled conditions. The assessment of polysaccharide regions available for conjugation process after the hydrolysis is crucial to predict the conjugation results for achieving the final active pharmaceutical ingredient. Two hydrolyzed capsular polysaccharides were analyzed by a heteronuclear single-quantum correlation experiment. It was adjusted for assessing 3JP-H to check the position of phosphate mono-ester residue after the hydrolysis process. All evaluated polysaccharides have been shown to remain with the anomeric position available for subsequent conjugation. The adjusted spectroscopic experiment was shown to be effective to study the hydrolysis of phosphate di-ester linked to capsular polysaccharides.

Obtención y caracterización de anticuerpos monoclonales contra polisacáridos capsulares de Streptococcus pneumoniae serotipo 1, 5, 6B, 14 y 19F

Obtención y caracterización de anticuerpos monoclonales contra polisacáridos capsulares de Streptococcus pneumoniae serotipo 1, 5, 6B, 14 y 19F

Identification of Group B Streptococcus Capsule Type by Use of a Dual Phenotypic/Genotypic Assay.

The group B streptococcus (GBS) capsular polysaccharide (CPS) is an important virulence factor which is also used for GBS typing. There are 10 CPS types (Ia, Ib, and II to IX). GBS that do not phenotypically type are considered nontypeable. All genes required for CPS synthesis are found on the GBS cps operon, which contains a highly variable CPS-determining region (cpsG-cpsK). The objective of this study was development of an assay to detect sialic acid on the GBS cell surface, followed by a genotypic PCR CPS typing assay. Sialic acid is located at the terminal end of the side chain of all known GBS CPS types. Sialic acid can be bound to commercially available lectins such as slug Limax flavus lectin. Biotinylated L. flavus-streptavidin-peroxidase complex was used in an enzyme immunoassay and dot blot assay to detect sialic acid. This was followed by a PCR typing scheme that was developed to target the serotype-determining region of the cps locus for Ia, Ib, and II to IX. Sialic acid from the CPS types Ia, Ib, and II to IX was detectable on the GBS cell surfaces of all previously identified CPS-typed GBS strains assayed. This was followed by the real-time PCR typing assay which successfully identified CPS Ia, Ib, and II to IX types. The combination of phenotypic and genotypic assays provides an accurate tool for detection of CPS expression and assignment of CPS typing. These assays have the potential to be used for CPS typing in large-scale epidemiological studies.

Comparison of molecular serotyping approaches of Streptococcus agalactiae from genomic sequences

BackgroundGroup B streptococcus (GBS) capsular polysaccharide is one of the major virulence factors underlying invasive GBS disease and a component of forthcoming vaccines. Serotype classification of GBS is based on the capsule polysaccharide of which ten variants are known to exist (Ia, Ib, II-IX). Current methods for GBS serotype assignment rely on latex agglutination or PCR while more recently a whole genome sequencing method was reported. In this study, three distinct algorithms for serotype assignment from genomic data were assessed using a panel of 790 clinical isolates.MethodsThe first approach utilised the entire capsular locus coupled with a mapping methodology. The second approach continues from the first and utilised a SNP-based methodology across the conserved cpsD-G region to differentiate serotypes Ia-VII and IX. Finally the third approach used the variable cpsG –K region coupled with a mapping methodology. All three approaches were assessed for typeability (percentage of isolates assigned a serotype) and concordance to the latex agglutination methodology.ResultsFollowing comparisons, the third approach using the variable cpsG-K region demonstrated the best performance with 99.9% typeability and 86.7% concordance. Overall, of the 105 discordant isolates, 71 were resolved following retesting of latex agglutination and whole genome sequencing, 20 failed to assign a serotype using latex agglutination and only 14 were found to be truly discordant on re-testing. Comparison of this final approach with the previously described assembly-based approach returned identical results.ConclusionsThese results demonstrated that molecular capsular typing using whole genome sequencing and a mapping-based approach is a viable alternative to the traditional, latex agglutination-based serotyping method and can be implemented in a public health microbiology setting.

Иммунохимические и протективные свойства конъюгированного капсульного полисахарида Streptococcus pneumoniae серотипа 9N

Иммунохимические и протективные свойства конъюгированного капсульного полисахарида Streptococcus pneumoniae серотипа 9N

Chemical Synthesis of the Repeating Unit of Type V Group B Streptococcus Capsular Polysaccharide.

The first chemical synthesis of the heptasaccharide repeating unit of type V group B Streptococcus capsular polysaccharide (CPS) by a preactivation-based one-pot [2 + 1 + 4] glycosylation strategy is described. The synthetic efficiency was further improved by using diol glycosyl acceptors for regio-/stereoselective glycosylation reactions. The synthetic target contains a free amino group at the reducing end, facilitating additional regioselective elaboration. The results should be useful for synthetic and biological studies of related CPSs.

Natural acquired group B Streptococcus capsular polysaccharide and surface protein antibodies in HIV-infected and HIV-uninfected children

Group B Streptococcus (GBS) is a major cause of invasive disease in young infants and also in older immunocompromised individuals, including HIV-infected persons. We compared naturally acquired antibody titres to GBS polysaccharide and surface protein antigens in HIV-uninfected and HIV-infected children aged 4–7 years.A multiplex Luminex immunoassay was used to measure IgG concentrations against GBS capsular polysaccharides (CPS) for serotypes Ia, Ib, III and V; and also extracellular localizing proteins which included cell-wall anchored proteins: Fibrinogen binding surface Antigen (FbsA), GBS Immunogenic Bacterial Adhesin (BibA), Surface immunogenic protein (Sip), gbs0393, gbs1356, gbs1539, gbs0392; and lipoproteins gbs0233, gbs2106 and Foldase PsrA.HIV-infected children (n=68) had significantly lower IgG GMT compared to HIV-uninfected (n=77) children against CPS of serotype Ib (p=0.012) and V (p=0.0045), and surface proteins Sip (p<0.001) and gbs2106 (p=0.0014). IgG GMT against GBS surface proteins: FbsA, gbs1539, gbs1356, gbs0392, gbs0393 and Foldase PsrA were significantly higher in HIV-infected children (p<0.004). Moreover, amongst HIV infected children, IgG GMT to GBS surface proteins were higher in those with CD4+ lymphocyte counts <500cell/μL compared to those who had CD4+ lymphocyte count ⩾500cell/μL with the exception of Sip.The increased susceptibility to invasive GBS disease in HIV-infected individuals could be due to the lower serotype specific capsular antibody and possibly due to lower antibody to some of the GBS proteins such as Sip and gbs2106.

The synthesis of the phosphate-bridged tetrasaccharide representing the repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 6B

GRAPHICAL ABSTRACT

Structure of the Type IX Group B Streptococcus Capsular Polysaccharide and Its Evolutionary Relationship with Types V and VII

The Group B Streptococcus capsular polysaccharide type IX was isolated and purified, and the structure of its repeating unit was determined. Type IX capsule → 4)[NeupNAc-α-(2 → 3)-Galp-β-(1 → 4)-GlcpNAc-β-(1 → 6)]-β-GlcpNAc-(1 → 4)-β-Galp-(1 → 4)-β-Glcp-(1 → appears most similar to types VII and V, although it contains two GlcpNAc residues. Genetic analysis identified differences in cpsM, cpsO, and cpsI gene sequences as responsible for the differentiation between the three capsular polysaccharide types, leading us to hypothesize that type V emerged from a recombination event in a type IX background.

Fine specificity and cross-reactions of monoclonal antibodies to group B streptococcal capsular polysaccharide type III

Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the dominant “protective” immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and cells. The results showed marked differences in the fine specificity among these mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and GT3 carbohydrates, representing structures found on surfaces of neural and developing cells, were demonstrated using carbohydrate array technology. The anti-CPSIII mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we serendipitously demonstrated cross-reactions of some anti-CPSIII mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen.

Persistence of functional antibodies to group B streptococcal capsular polysaccharides following immunization with glycoconjugate vaccines

The duration of functional activity of group B streptococcal (GBS) glycoconjugate vaccine-induced capsular polysaccharide-specific (CPS) IgG was evaluated among healthy adult responders. Opsonophagocytic activity declined significantly from a 4-week post-immunization peak, but substantial functional activity, exceeding 1log10 reduction in GBS cfu/mL, was retained at 18 months to 2 years post-immunization for each GBS type assessed. The persistence of functional antibody activity when GBS CPS-specific IgG concentrations decline, although remaining significantly higher than pre-immunization levels, suggests that long-term protection may be expected from candidate GBS glycoconjugates administered to this population.