Nanoparticles as Delivery Systems for Antigenic Saccharides: From Conjugation Chemistry to Vaccine Design

Abstract

Glycoconjugate vaccines have been effective in preventing numerous bacterial infectious diseases and have shown recent potential to treat cancers through active immunotherapy. Soluble polysaccharides elicit short-lasting immune responses and are usually covalently linked to immunogenic carrier proteins to enhance the antigen-specific immune response by stimulating T-cell-dependent mechanisms. Nonetheless, the conjugation of purified polysaccharides to carrier proteins complexifies vaccine production, and immunization with protein glycoconjugates can lead to the undesirable immunogenic interference of the carrier. Recently, the use of nanoparticles and nanoassemblies for the delivery of antigenic saccharides has gathered attention from the scientific community. Nanoparticles can be easily functionalized with a diversity of functionalities, including T-cell epitope, immunomodulator and synthetic saccharides, allowing for the modulation and polarization of the glycoantigen-specific immune response. Notably, the conjugation of glycan to nanoparticles protects the antigens from degradation and enhances their uptake by immune cells. Different types of nanoparticles, such as liposomes assembled from lipids, inorganic nanoparticles, virus-like particles and dendrimers, have been explored for glycovaccine design. The versatility of nanoparticles and their ability to induce robust immune responses make them attractive delivery platforms for antigenic saccharides. The present review aims at summarizing recent advancements in the use of nano-scaled systems for the delivery of synthetic glycoantigens. After briefly presenting the immunological mechanisms required to promote a robust immune response against antigenic saccharides, this review will offer an overview of the current trends in the nanoparticle-based delivery of glycoantigens.

Keywords: antigens; conjugation; glycoconjugates; immune responses; liposomes; nanocarriers; nanoparticles; polysaccharides; vaccines.

Figure 1

Schematic representation of the immune processing of (A) polysaccharides and (B) glycoconjugates leading to cytokine production and antibody secretion. Glycoconjugates can be processed intracellularly and are displayed as glycopeptides on B-cell via MHC II, allowing for recognition by T-cells. Co-stimulation between B- and T-cells leads to cytokine release and B-cell activation. This T-cell-dependent response generates high-affinity, class-switched antibodies and memory cells. BCR: B-cell receptor; MHC: Major histocompatibility complex; TCR: T-cell receptor; IL: Interleukin. (C) Schematic representation of glycoconjugate nanoparticles. (1) Liposomes that can incorporate immune activators such as Pam2, Pam3, alpha galactosylceramide, and MPLA. (2) Gold nanoparticles. (3) Virus-like particles, such as bacteriophage Q beta (PDB: 1QBE). (4) Dendrimers such as tetravalent lysine core dendrimer, represented here with N-acetylgalactosamine.

Figure 2

Overview of the strategies for glycan antigens’ chemical conjugation to nanocarriers. EDC: 1-ethyl-3(3-dimethylaminopropyl)carbodiimide; NHS: sulfo-N-hydroxysuccinimide.