Synthesis, Conformal Analysis, and Antibody Binding of Staphylococcus aureus Capsular Polysaccharide Type 5 Oligosaccharides.

Staphylococcus aureus is one of the most prominent pathogens responsible for life-threatening hospital acquired infections. Most clinical isolates belong to serotype 5 or 8, which express unique capsular polysaccharides (CP), composed of the rare N-acetyl-β-d-mannosaminuronic acid (β-d-ManNAcA), N-acetyl-α-l-fucosamine (α-l-FucNAc) and N-acetyl-β-d-fucosamine (β-d-FucNAc) that can be used for the development of conjugate vaccines. Different acetylation patterns of CP5 create microheterogeneous polymers, carrying partial zwitterionic character, which may be important for immunological activity.

Multimeric, multivalent fusion carrier proteins for site-selective glycoconjugate vaccines simultaneously targeting and .

and are major antimicrobial-resistant pathogens that often synergize in polymicrobial infections, such as chronic wound infections. These notorious and increasingly resistant bacteria contribute significantly to reduced antibiotic efficacy. Despite their substantial clinical burden, the urgent need to combat bacterial resistance and extensive research efforts, no vaccines currently exist for either bacterium.

Long, Synthetic Type 8 Capsular Oligosaccharides Reveal Structural Epitopes for Effective Immune Recognition.

is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the cell wall and have been proposed as promising candidate antigens.

Semisynthetic Glycoconjugates as Potential Vaccine Candidates Against Haemophilus influenzae Type a.

Glycoconjugate vaccines are based on chemical conjugation of pathogen-associated carbohydrates with immunogenic carrier proteins and are considered a very cost-effective way to prevent infections. Most of the licensed glycoconjugate vaccines are composed of saccharide antigens extracted from bacterial sources. However, synthetic oligosaccharide antigens have become a promising alternative to natural polysaccharides with the advantage of being well-defined structures providing homogeneous conjugates.

Antigenic determinants driving serogroup-specific antibody response to Neisseria meningitidis C, W, and Y capsular polysaccharides: Insights for rational vaccine design.

Meningococcal glycoconjugate vaccines sourced from capsular polysaccharides (CPSs) of pathogenic Neisseria meningitidis strains are well-established measures to prevent meningococcal disease. However, the exact structural factors responsible for antibody recognition are not known. CPSs of Neisseria meningitidis serogroups Y and W differ by a single stereochemical center, yet they evoke specific immune responses.

A Multidisciplinary Structural Approach to the Identification of the Type b Capsular Polysaccharide Protective Epitope.

Glycoconjugate vaccines so far licensed are generally composed of a native or size-reduced capsular polysaccharide conjugated to carrier proteins. Detailed information on the structural requirements necessary for CPS recognition is becoming the key to accelerating the development of next-generation improved glycoconjugate vaccines. Structural glycobiology studies using oligosaccharides (OS) complexed with functional monoclonal antibodies represent a powerful tool for gaining information on CPS immunological determinants at the atomic level.

Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance.

Antimicrobial resistance (AMR) is one of the most critical threats to global public health in the 21st century, causing a large number of deaths every year in both high-income and low- and middle-income countries. Vaccines and monoclonal antibodies can be exploited to prevent and treat diseases caused by AMR pathogens, thereby reducing antibiotic use and decreasing selective pressure that favors the emergence of resistant strains. Here, differences in the mechanism of action and resistance of vaccines and monoclonal antibodies compared to antibiotics are discussed.

Glycoconjugate vaccines against antimicrobial resistant pathogens.

Introduction: Antimicrobial resistance (AMR) is responsible for the death of millions worldwide and stands as a major threat to our healthcare systems, which are heavily reliant on antibiotics to fight bacterial infections. The development of vaccines against the main pathogens involved is urgently required as prevention remains essential against the rise of AMR.

Areas Covered: A systematic research review was conducted on MEDLINE database focusing on the six AMR pathogens defined as ESKAPE (, , , , , and ), which are considered critical or high priority pathogens by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC).

Proof of concept for a single-dose Group B Streptococcus vaccine based on capsular polysaccharide conjugated to Qβ virus-like particles.

A maternal vaccine to protect neonates against Group B Streptococcus invasive infection is an unmet medical need. Such a vaccine should ideally be offered during the third trimester of pregnancy and induce strong immune responses after a single dose to maximize the time for placental transfer of protective antibodies. A key target antigen is the capsular polysaccharide, an anti-phagocytic virulence factor that elicits protective antibodies when conjugated to carrier proteins.

Outer Membrane Vesicle Vaccine Platforms.

Outer membrane vesicles (OMVs) are spontaneously released by many gram-negative bacteria during their growth and constitute an important virulence factor for bacteria, helping them to survive through harsh environmental conditions. Native OMVs, naturally-released from bacteria, are produced at a level too low for vaccine manufacturing, requiring chemical treatment (detergent-extracted) or genetic manipulation, resulting in generalized modules for membrane antigens (GMMAs). Over the years, the nature and properties of OMVs have made them a viable platform for vaccine development.

Strengths and weaknesses of pneumococcal conjugate vaccines.

Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use of polysaccharide-protein conjugate vaccines has been pivotal in reducing the incidence of invasive pneumococcal disease despite the emergence of non-vaccine serotypes. Notwithstanding its undoubtable success, some weaknesses have called for continuous improvement of pneumococcal vaccination.

Chemical Synthesis and Immunological Evaluation of Fragments of the Multiantennary Group-Specific Polysaccharide of Group B .

Group B (GBS) is a Gram-positive bacterium and the most common cause of neonatal blood and brain infections. At least 10 different serotypes exist, that are characterized by their different capsular polysaccharides. The Group B carbohydrate (GBC) is shared by all serotypes and therefore attractive be used in a glycoconjugate vaccine.

Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance.

Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria , , , , , , , non-typhoidal , and , and the fungus , have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B , are classified as concerning threats.

Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for the effectiveness of glycoconjugate vaccine candidates.

The introduction of glycoconjugate vaccines marks an important point in the fight against various infectious diseases. The covalent conjugation of relevant polysaccharide antigens to immunogenic carrier proteins enables the induction of a long-lasting and robust IgG antibody response, which is not observed for pure polysaccharide vaccines. Although there has been remarkable progress in the development of glycoconjugate vaccines, many crucial parameters remain poorly understood.

Recent advances and future perspectives on carbohydrate-based cancer vaccines and therapeutics.

Carbohydrates are abundantly expressed on the surface of both eukaryotic and prokaryotic cells, often as post translational modifications of proteins. Glycoproteins are recognized by the immune system and can trigger both innate and humoral responses. This feature has been harnessed to generate vaccines against polysaccharide-encapsulated bacteria such as Streptococcus pneumoniae, Hemophilus influenzae type b and Neisseria meningitidis.

Elucidating the Structural and Minimal Protective Epitope of the Serogroup X Meningococcal Capsular Polysaccharide.

Despite the considerable progress toward the eradication of meningococcal disease with the introduction of glycoconjugate vaccines, previously unremarkable serogroup X has emerged in recent years, recording several outbreaks throughout the African continent. Different serogroup X polysaccharide-based vaccines have been tested in preclinical trials, establishing the principles for further improvement. To elucidate the antigenic determinants of the MenX capsular polysaccharide, we generated a monoclonal antibody, and its bactericidal nature was confirmed using the rabbit serum bactericidal assay.

Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models.

Nanoparticle systems are being explored for the display of carbohydrate antigens, characterized by multimeric presentation of glycan epitopes and special chemico-physical properties of nano-sized particles. Among them, outer membrane vesicles (OMVs) are receiving great attention, combining antigen presentation with the immunopotentiator effect of the Toll-like receptor agonists naturally present on these systems. In this context, we are testing Generalized Modules for Membrane Antigens (GMMA), OMVs naturally released from Gram-negative bacteria mutated to increase blebbing, as carrier for polysaccharides.

Broadening the concept of glycoconjugates: glycoRNA and ubiquitinylated lipopolysaccharide.

Two recent papers ( https://doi.org/10.1016/j.

Lipid-Based Nanoparticles for Delivery of Vaccine Adjuvants and Antigens: Toward Multicomponent Vaccines.

Despite the many advances that have occurred in the field of vaccine adjuvants, there are still unmet needs that may enable the development of vaccines suitable for more challenging pathogens (e.g., HIV and tuberculosis) and for cancer vaccines.

Glycoconjugate vaccines: classic and novel approaches.

Glycoconjugate vaccines, obtained by carbohydrates covalently bound to protein carriers, have contributed to fight diseases such as meningitidis, pneumonia and typhoid fever. Despite new technologies such as RNA and adenovirus based vaccine have now reached the market, these approaches are unable to target carbohydrates which are key virulence factors.This issue intends to provide an overview on relevant directions where the field is evolving and serve as starting point to increase interest in this exciting and fundamental part of vaccinology.

Carbohydrate based meningococcal vaccines: past and present overview.

Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive strains are surrounded by a polysaccharide capsule, based on which, 12 N.