Search Results (251)

A rational synthesis of the branched decaarabinofuranoside with 4-(2-azidoethoxy)phenyl aglycone (a Janus aglycone) related to the non-reducing terminal fragments of the arabinogalactan and lipoarabinomannan from Mycobacterium tuberculosis was proposed. Since the most challenging step is the formation of a 1,2-cis glycosidic linkage, we have significantly simplified access to a library of oligoarabinofuranosides derived from Mycobacterium tuberculosis polysaccharides using a silylated Ara-β-(1→2)-Ara disaccharide as the glycosyl donor. The application of a Janus aglycone also allowed us to reduce the number of reaction steps in glycoside synthesis. The obtained arabinans can be useful to further prepare conjugates as antigens for creating tuberculosis screening assays. Full article

Biogenic silver nanoparticles (AgNPs) were synthesized via a green chemistry strategy using wheat extract and subsequently functionalized with a carboxymethyl chitosan–cinnamaldehyde (CMC=CIN) conjugate through covalent imine bonding. The resulting nanohybrid (AgNP–CMC=CIN) was extensively characterized to confirm successful biofunctionalization: UV–Vis spectroscopy revealed characteristic cinnamaldehyde absorption peaks; ATR-FTIR spectra confirmed polymer–terpene bonding; and TEM analysis evidenced uniform nanoparticle morphology. Dynamic light scattering (DLS) measurements indicated an increase in hydrodynamic size upon coating (from 59.46 ± 12.63 nm to 110.17 ± 4.74 nm), while maintaining low polydispersity (PDI: 0.29 to 0.27) and stable surface charge (zeta potential ~ −30 mV), suggesting colloidal stability and homogeneous polymer encapsulation. Antifungal activity was evaluated against Fusarium oxysporum, Penicillium citrinum, Aspergillus niger, and Aspergillus brasiliensis. The minimum inhibitory concentration (MIC) against F. oxysporum was significantly reduced to 83 μg/mL with AgNP–CMC=CIN, compared to 708 μg/mL for uncoated AgNPs, and was comparable to the reference fungicide tebuconazole (52 μg/mL). Seed priming with AgNP–CMC=CIN led to improved germination (85%) and markedly reduced fungal colonization, while maintaining a favorable phytotoxicity profile. These findings highlight the potential of polysaccharide-terpene-functionalized biogenic AgNPs as a sustainable alternative to conventional fungicides, supporting their application in precision agriculture and integrated crop protection strategies. Full article

This review focuses on the synthesis of spacer-armed phosphooligosaccharides structurally related to the capsular phosphoglycans of pathogenic bacteria, including the Haemophilus influenzae serotypes a, b, c, and f, Neisseria meningitidis serogroups a and x, the Streptococcus pneumoniae serotypes 6a, 6b, 6c, 6f, 19a, and 19f, and the Campylobacter jejuni serotype HS:53, strain RM1221, in which the phosphodiester linkage is a structural component of a phosphoglycan backbone. Also, in this review, we summarize the current knowledge on the preparation and immunogenicity of neoglycoconjugates based on synthetic phosphooligosaccharides. The discussed data helps evaluate the prospects for the development of conjugate vaccines on the basis of synthetic phosphooligosaccharide antigens. Full article

Global concerns about environmental pollution, poor waste management, and the rise in antimicrobial resistance due to uncontrolled antibiotic use have driven researchers to seek alternative, multifaceted solutions. Plants, animals, microorganisms, and their processing wastes serve as valuable sources of natural biopolymers and bioactive compounds. Through nanotechnology, these can be assembled into formulations with enhanced antimicrobial properties, high safety, and low toxicity. This review explores polysaccharides, including chitosan, alginate, starch, pectin, cellulose, hemicellulose, gums, carrageenan, dextran, pullulan, and hyaluronic acid, used in nanotechnology, highlighting their advantages and limitations as nanocarriers. Addressing the global urgency for alternative antimicrobials, we examined natural compounds derived from plants, microorganisms, and animals, such as phytochemicals, bacteriocins, animal antimicrobial peptides, and proteins. Focusing on their protection and retained activity, this review discusses polysaccharide-based nanoformulations with natural antimicrobials, including nanoparticles, nanoemulsions, nanocapsules, nanoplexes, and nanogels. Special emphasis is placed on strategies and formulations for the encapsulation, entrapment, and conjugation of natural compounds using polysaccharides as protective carriers and delivery systems, including a brief discussion on their future applications, prospects, and challenges in scaling up. Full article

Purpose: This study aimed to evaluate the immunological response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) in patients investigated for immunodeficiencies due to recurrent infections at EPM-UNIFESP Clinical Immunology outpatient clinic. Methods: This is a longitudinal retrospective study. Data were collected from the medical records of patients between 2012 and 2020. The analyses were developed in two stages: before and after administration of the PPV23 vaccine. Results: A total of 390 patients who received the PPV23 vaccine were selected. Among those who demonstrated an adequate serological response (63.6%), there was a notable decrease in the risk of upper respiratory tract infections (URTI) by 66%, tonsillitis by 74%, otitis by 76%, sinusitis by 49%, and uncomplicated pneumonia (PNM) by 77%. For invasive infections, the risk reduction was 95% for pneumonia with parapneumonic effusion and 93% for meningitis. Conclusions: The study demonstrated a significant decrease in the risk of bacterial infections following the administration of the PPV23 vaccine in this population. Therefore, we recommend including PPV23 in the vaccination schedule following pneumococcal conjugated vaccines for patients with recurrent pneumococcal infections to enhance protection and avoid complications. Full article

Background: The introduction of biological drugs into clinical practice for the treatment of children with systemic juvenile idiopathic arthritis (sJIA) allows disease control but increases the risk of infectious events. Infectious events cause immunosuppressive therapy interruptions, leading to disease flare and life-threatening complications, namely macrophage activation syndrome. Our study aimed to evaluate the efficacy and safety of simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) in children with sJIA. Methods: This study included 100 sJIA patients receiving immunosuppressive therapy who were simultaneously vaccinated against pneumococcal and Haemophilus influenzae type b (Hib) infections. The mean age of disease onset was 5.5 years. The median age at vaccination was 10 ± 4.5 years. Clinical and laboratory parameters of sJIA activity, immunization efficacy, and safety, including anti-SP and anti-Hib IgG antibodies, as well as all vaccination-related adverse events (AEs), were recorded in every patient before, 3 weeks after, and 6 months after vaccination. Results: At the time of vaccination, 29% of patients did not meet the criteria for the inactive disease stage, as defined by C. Wallace: active joints were present in 34.5% of patients, systemic manifestations (rash and/or fever) were present in 41.3%, and 24.2% of patients had solely inflammatory laboratory activity. The protective titer of anti-SP and anti-Hib IgG antibodies was detected in the majority of patients 3 weeks after vaccination (100% and 93%, respectively). The results remained unchanged (99% and 92%, respectively) for 6 months of follow-up, compared to the baseline (91% and 37%, p = 0.000001). Anti-SP IgG and anti-Hib titers raised from 48.3 (18.2; 76.5) and 0.64 (0.3; 3.2) U/mL at the baseline to 103.5 (47.3; 185.4) and 4 (3.5; 4.2) U/mL at D22 and 105 (48.7; 171.8) and 4 (3.8; 4) U/mL (EOS), respectively. Immunosuppressive therapy regimens (combined therapy or biological disease-modifying antirheumatic drug monotherapy) did not influence the immunogenic efficacy of vaccination. The incidence of infectious complications (p = 0.0000001) and antibiotic prescriptions (p = 0.0000001) decreased by more than two times, to 29.9 and 13.8 events per 100 patient months, respectively, within 6 months after vaccination—the average duration of acute infectious events was reduced by five times after immunization (p = 0.0000001). Vaccination did not lead to disease flare: the number of patients with active joints decreased by half compared to the baseline, and the number of patients with systemic manifestations decreased by six times. All vaccine-associated adverse events were considered mild and resolved within 1–2 days. Conclusions: Simultaneous vaccination against pneumococcal and Hib infections in sJIA children is an effective and safe tool that reduces the number and duration of infectious events and does not cause disease flare-ups. Full article

The covalent interactions of polysaccharides and protein can improve the emulsification and stability of Pickering emulsions, which are promising systems for the delivery of active substances. Okra flowers, which commonly represent agricultural waste, have high-viscosity polysaccharides that can be used for the development of protein–polysaccharide-based emulsifiers. In this study, the Maillard reaction was performed under optimized conditions (70 °C, pH 10, and 12 h) with a 1:1 mass ratio to generate pea protein isolate (PPI)–okra flower polysaccharide (OP) conjugate with the highest grafting degree of 22.80 ± 0.26%. The covalent binding of OP facilitated variations in the secondary and tertiary structures of PPI, decreasing its particle size (from 535.70 to 212.05 nm) and zeta-potential (from −30.37 to −44.39 mV). The emulsifying stability of the emulsion stabilized by OP-PPI conjugates was significantly improved due to the formation of a stable interfacial layer, showing an 80.39% increase compared to that of free PPI. Simultaneously, the emulsions prepared with the conjugates demonstrated excellent stability across diverse environmental conditions by enhancing the interaction between the lipid and protein. Moreover, the conjugate-stabilized emulsion not only exhibited a higher encapsulation efficiency of 91.52 ± 0.75% and superior protective efficacy but also controlled the release of apigenin (API) during gastrointestinal digestion, achieving the highest API bioaccessibility (74.58 ± 1.19%). Furthermore, it also contributed to the absorption and transmembrane transport efficiency of API in Caco-2 cells, improving its bioavailability. These results confirmed that covalent conjugation with OP is a valuable strategy for enhancing the emulsifying features of PPI. The PPI–OP emulsion delivery system holds great potential for nutrient delivery. Full article

Background: The aging of the population has increased the number of frail people living in long-term care facilities, underscoring the need for continuous updates in infectious diseases prevention strategies. The aim of this study was to analyze two pneumococcal disease outbreaks in elderly residences in Gipuzkoa, northern Spain, their impact on residents, and the containment measures implemented. Material and methods: The outbreaks took place in 2023 and in 2024 in two residences of 111 and of 155 residents, respectively. Diagnosis was based on clinical criteria, radiological findings, and microbiological techniques. Pneumococcal isolates were characterized by whole-genome sequencing. Results: The outbreaks involved five and six residents, respectively. Most residents in both facilities had been vaccinated with the pneumococcal polysaccharide 23-valent vaccine (PPV23) more than five years prior. The median attack rates were 4.5% and 3.9%, lower than those reported in similar outbreaks. The adopted infection transmission prevention measures successfully limited the spread of the outbreaks. Conclusions: PPV23 vaccination did not prevent invasive pneumococcal infection in the affected residents. The vaccination of elderly people living in long-term care facilities with 20-valent and 21-valent pneumococcal conjugated vaccines should be evaluated as a new preventive measure. Full article

Escherichia coli and Klebsiella pneumoniae are major contributors to the global challenge of antimicrobial resistance, posing serious threats to public health. Among current preventive strategies, conjugate vaccines that utilize bacterial surface polysaccharides have emerged as a promising and effective approach to counter multidrug-resistant strains. In this study, both the Wzy/Wzx-dependent and ABC transporter-dependent biosynthetic pathways for antigenic polysaccharides were introduced into E. coli W3110 cells. This dual-pathway engineering enabled the simultaneous biosynthesis of two structurally distinct polysaccharides within a single host, offering a streamlined and potentially scalable strategy for vaccine development. Experimental findings confirmed that both polysaccharide types were successfully produced in the engineered strains, although co-expression levels were moderately reduced. A weak competitive interaction was noted during the initial phase of induction, which may be attributed to competition for membrane space or the shared use of activated monosaccharide precursors. Interestingly, despite a reduction in plasmid copy number and transcriptional activity of the biosynthetic gene clusters over time, the overall polysaccharide yield remained stable with prolonged induction. This suggests that extended induction does not adversely affect final product output. Additionally, two glycoproteins were efficiently generated through in vivo bioconjugation of the synthesized polysaccharides with carrier proteins, all within the same cellular environment. This one-cell production system simplifies the workflow and enhances the feasibility of generating complex glycoprotein vaccines. Whole-cell proteomic profiling followed by MFUZZ clustering and Gene Ontology analysis revealed that core biosynthetic genes were grouped into two functional clusters. These genes were predominantly localized to the cytoplasm and were enriched in pathways related to translation and protein binding. Such insights not only validate the engineered biosynthetic routes but also provide a molecular basis for optimizing future constructs. Collectively, this study presents a robust synthetic biology platform for the co-expression of multiple polysaccharides in a single bacterial host. The approach holds significant promise for the rational design and production of multivalent conjugate vaccines targeting drug-resistant pathogens. Full article

Background/Objectives: The clinical impact of replacing the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the vaccination of older (≥60 years) and at-risk German adults with either the 20-valent (PCV20) or 21-valent (V116) pneumococcal conjugate vaccine (PCV) was evaluated. Methods: An age- and serotype-specific transmission model was adapted to Germany to evaluate the impact of V116 versus PCV20 vaccination on pneumococcal disease (PD) incidence, including invasive pneumococcal disease (IPD) and inpatient and outpatient non-bacteremic pneumococcal pneumonia, over 10 years. A reference strategy (PPSV23 vaccination at a constant 30% vaccine coverage rate (VCR)) was compared against eight strategies varying by PCV (PCV20 vs. V116), VCR (30% vs. 60%), with or without the PCV revaccination of previously PPSV23-vaccinated adults (0% vs. 50% revaccination). Results: Vaccination with PCV20 and V116 initially decreased PD incidence, but incidence returned to pre-vaccine levels after five and eight years, respectively. Increasing the VCR to 60% prevented this resurgence. At a 10-year time horizon, V116 with 30% VCR reduced IPD cases by 9%, inpatient NBPP cases by 10%, and outpatient NBPP cases by 7% compared to the reference strategy. PCV20 with 30% VCR reduced these cases by 6%, 5%, and 4%, respectively. Increasing the VCR to 60% and revaccinating 50% of previously PPSV23-vaccinated adults further reduced IPD cases by 14% and 13% for V116, and by 9% and 9% for PCV20. Conclusions: Increasing the vaccination coverage rate to 60% and strategically revaccinating previously PPSV23-vaccinated adults significantly enhanced the effectiveness of pneumococcal vaccines, with V116 showing greater overall reductions in disease incidence compared to PCV20 or PPSV23. Full article

Enteric fever is caused by Salmonella enterica serovar Typhi (S. Typhi) and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B, and C. Globally, an estimated 11 to 21 million cases of typhoid and paratyphoid fever occur annually, with approximately 130,000–160,000 deaths, most of which are reported in South/Southeast Asia and sub-Saharan Africa. The antibiotic susceptibility of S. Typhi strains varies between countries within broad limits, from 3% to 97% for ampicillin, 9% to 95% for ciprofloxacin, 4% to 94% for chloramphenicol (India vs. Pakistan), and 0% to 99% for ceftriaxone (India vs. Iraq). With S. Typhi increasingly exhibiting resistance to antibiotics, vaccination becomes an essential preventive measure. Currently, three vaccines are licensed for typhoid fever: the typhoid conjugate vaccine (TCV), live-attenuated oral vaccine Ty21a (Ty21a), and Vi capsular polysaccharide vaccine (Vi-CPS). While no specific vaccine exists for paratyphoid fever, the genetic and antigenic similarities between S. Paratyphi and S. Typhi offer potential for the development of such a vaccine. Early studies show promising results, demonstrating both safety and immunogenicity in preclinical trials. Whole genome sequencing (WGS) provides a powerful tool for assigning genotypes, identifying plasmids, comparing genetic elements, and investigating molecular factors that contribute to antibiotic resistance and virulence. Full article

Oligosaccharides and glycoconjugates play essential roles in various biological processes such as cellular recognition and signaling, and thus have attracted tremendous attention in the synthetic and biological communities over the past few decades. Contributing to this field, we have achieved the synthesis of the aminoxyglycoside pentasaccharide subunit of Pseudomonas aeruginosa polysaccharide synthesis locus (Psl) exopolysaccharide through an efficient 23 step process. This pentasaccharide was designed with an aminooxy derivative at the reducing end, which was used in a 2-step oxime-based bioconjugation to the protein carrier CRM197, with an epitope ratio of 1:4. The conjugate vaccine could generate anti-Psl antibodies that could recognize P. aeruginosa PAO1 bacteria and initiate opsonophagocytic killing of the bacteria. In addition, the aminoxyglycoside could be conveniently conjugated to a bifunctional aldehyde-biotin reagent, which can be used for quantifying antibody titers in vaccination studies. Full article

Background: V116 is a 21-valent pneumococcal conjugate vaccine (PCV) designed for adults. It contains the most prevalent serotypes associated with invasive pneumococcal disease (IPD) in adults in regions with established pediatric vaccination programs. This Phase 3 study compared the safety, tolerability, and immunogenicity of V116 with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults ≥50 years of age. Methods: In this randomized, active comparator-controlled, parallel-group, multisite, double-blind study, participants were randomized 1:1 to receive a single dose of V116 or PPSV23 (NCT05569954). Primary immunogenicity outcomes assessed the opsonophagocytic activity (OPA) responses for (i) non-inferiority for 12 serotypes common to V116 and PPSV23 based on V116/PPSV23 geometric mean titers (GMTs) at Day 30, and (ii) superiority for nine serotypes unique to V116 using V116/PPSV23 GMTs and the proportions of participants with a ≥4-fold rise in OPA responses from baseline to 30 days post-vaccination. The primary safety outcome was evaluated as the proportion of participants with solicited injection-site and systemic adverse events through Day 5 post-vaccination, and vaccine-related serious adverse events up to 6 months post-vaccination. Findings: V116 was non-inferior to PPSV23 for all 12 common serotypes, superior to PPSV23 for all nine unique serotypes based on V116/PPSV23 GMTs, and superior to PPSV23 for eight of the nine serotypes unique to V116, based on the proportion of participants with a ≥4-fold rise in OPA responses (except for serotype 15C). The safety profile of V116 was comparable to that of PPSV23. Interpretation: In regions with established vaccination programs, V116 could broaden the serotype coverage for residual pneumococcal disease in adults. Full article

Prediabetes (pre-DM) is the buffer period before developing overt type 2 diabetes (T2DM), and the search for novel food agents to protect against pre-DM is in high demand. Our team previously reported that the Grifola frondosa (maitake mushroom) polysaccharide F2 reduced insulin resistance in T2DM rats induced by streptozocin (STZ) combined with a high-fat diet (HFD). This study aimed to evaluate the effects of G. frondosa polysaccharide F2 on disordered lipid and glucose metabolism and to investigate its mechanisms in pre-DM mice. F2 (30 and 60 mg/kg/d) was administered (i.g.) for 5 weeks to pre-DM mice. The results showed that F2 decreased the fasting blood glucose and lipid profile index of pre-DM mice (p < 0.05 or 0.0001). An untargeted metabolomics analysis of feces from pre-DM mice showed that F2 reduced the content of conjugated bile acids, including taurochenodeoxycholic acid and taurocholic acid, and increased the free bile acids of lithocholic acid. The results of 16S rDNA sequencing of feces from pre-DM mice showed that bile salt hydrolase (BSH)-producing bacteria, including Bacillus, Bifidobacterium, and Lactococcus, may be the therapy targets of F2 in pre-DM mice. Through the integrated analysis of untargeted metabolomics and 16S rDNA sequencing, it was found that F2 may ameliorate glucose and lipid metabolism disorders by promoting bile acid metabolism while regulating the abundance of BSH-producing bacteria (Lactococcus spp.), suggesting its potential as a functional food ingredient for the prevention of T2DM. Full article

Background/objectives: Streptococcus agalactiae (or Group B Streptococcus, GBS) is a major cause of neonatal meningitis globally. There are 10 serotypes of GBS, which are distinguished by their capsular polysaccharide (CPS) structure, with serotypes Ia, Ib, II, III, IV and V responsible for up to 99% of infections. Currently, there are no licensed vaccines against GBS. The most developed candidates are glycoconjugate vaccines, which can be highly effective but are also expensive to produce by existing approaches and unaffordable for many parts of the world. Biosynthesis of recombinant glycans and glycoconjugates in tractable strains of bacteria offers a low-cost alternative approach to current chemical conjugation methods. Methods: In this study, we apply combinatorial hierarchical DNA assembly to the heterologous biosynthesis of GBS III, IV and V CPSs in E. coli. Each gene was removed from its native regulation, paired with synthetic regulatory elements and rebuilt from the bottom up to generate libraries of reconstituted pathways. These pathways were screened for glycan biosynthesis using serotype-specific antisera. Results: We identified several configurations that successfully biosynthesised the GBS CPSs. Furthermore, we exploited the conserved nature of the GBS CPS biosynthesis loci and the flexibility of modular DNA assembly by constructing hybrid pathways from a minimal pool of glycosyltransferase genes. We show that transferase genes with homologous function can be used interchangeably between pathways, obviating the need to clone a complete locus for each new CPS assembly. Conclusions: In conclusion, we report the first demonstration of heterologous GBS CPS IV and V biosynthesis in E. coli, a key milestone towards the development of low-cost recombinant multivalent GBS glycoconjugate vaccines. Full article