Clostridium difficile is emerging worldwide as a major cause of nosocomial infections. The negatively charged PSII polysaccharide has been found in different strains of C. difficile and, thereby, represents an important target molecule for a possible carbohydrate-based vaccine. In order to identify a synthetic fragment that after conjugation to a protein carrier could be able to induce anti-PSII antibodies, we exploited a combination of chemical synthesis with immunochemistry, confocal immunofluorescence microscopy, and solid state NMR. We demonstrate that the phosphate group is crucial in synthetic glycans to mimic the native PSII polysaccharide; both native PSII and a phosphorylated synthetic hexasaccharide repeating unit conjugated to CRM(197) elicit comparable immunogenic responses in mice. This finding can aid design and selection of carbohydrate antigens to be explored as vaccine candidates.
Despite the enormous progress achieved by modern medicine, numerous diseases still have a profound impact on public health. Infectious diseases caused by a variety of microorganisms (viruses, fungi and parasites) and bacteria are a global major concern and, because of the emergence, for instance, of multidrug resistance, not only in developing countries. The development of preventative therapies, such as the rational design of novel and more efficient vaccines, might offer a solution to this state of affairs and other associated drawbacks. Vaccination is considered by the World Health Organization to be the most cost‐effective strategy for controlling infectious disease, because it should confer long‐term protective immunity in the population. A second consideration involves cancer. The outstanding progress achieved in the identification and structural characterization of tumour‐associated antigens has prompted their employment in tumour immunotherapy, on the basis of the observation that tumour cells possess specific antigens that can be recognized by an immune system appropriately conditioned to the task. Carbohydrates play key roles in many molecular recognition phenomena and they can affect any kind of interaction with the immune system. Saccharide‐based antigens (bacterial capsular polysaccharides or tumour‐associated carbohydrate antigens, for instance) have therefore been studied and employed in the formulation of vaccines. In recent years there has been increasing use of synthetic saccharide antigens for the formulation of vaccine candidates. These structures are indeed chemically well defined, devoid of biologic contaminants and, in principle, available in large amounts, relative to materials extracted from natural sources. In addition, synthetic saccharide antigens can also serve as haptens in protein conjugates, eliciting highly specific antibodies in animal models and humans. The great potential of synthetic saccharide antigens is attested to by the spectacular success of the Cuban vaccine against Haemophilus influenzae type b. Here we review the major advances in the development of synthetic carbohydrate‐based vaccines targeted against infectious diseases and cancer.
A protocol is reported for the preparation of water-soluble, thiol-protected Au nanoparticles (Au-MPC) where dioctylamine is used as a stabilizing agent when the gold cluster is formed using the two-phase Brust and Schiffrin procedure. The amount of amine controls the size of the nanoparticles in the 1.9-8.9 nm diameter range. The final stabilization of the gold clusters by addition of functionalized thiols is performed under very mild conditions compatible with most biomolecules. The procedure is suitable for a wide variety of functional groups present in the thiol and allows one to use thiol mixtures with a precise control of their composition in the monolayer. As a proof of principle, examples of nanoparticles protected with thiols comprising functional groups ranging from polyethers, saccharides, polyamines and ammonium ions are reported.
During the last decade there has been a growing interest in glycoimmunology, a relatively new research field dealing with the specific interactions of carbohydrates with the immune system. Pathogens’ cell surfaces are covered by a thick layer of oligo- and polysaccharides that are crucial virulence factors, as they mediate receptors binding on host cells for initial adhesion and organism invasion. Since in most cases these saccharide structures are uniquely exposed on the pathogen surface, they represent attractive targets for vaccine design. Polysaccharides isolated from cell walls of microorganisms and chemically conjugated to immunogenic proteins have been used as antigens for vaccine development for a range of infectious diseases. However, several challenges are associated with carbohydrate antigens purified from natural sources, such as their difficult characterization and heterogeneous composition. Consequently, glycoconjugates with chemically well-defined structures, that are able to confer highly reproducible biological properties and a better safety profile, are at the forefront of vaccine development. Following on from our previous review on the subject, in the present account we specifically focus on the most recent advances in the synthesis and preliminary immunological evaluation of next generation glycoconjugate vaccines designed to target bacterial and fungal infections that have been reported in the literature since 2011.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.