Chemical Biology Approaches to Designing Defined Carbohydrate Vaccines

Abstract

Carbohydrate antigens have shown promise as important targets for developing effective vaccines and pathogen detection strategies. Modifying purified microbial glycans through synthetic routes or completely synthesizing antigenic motifs are attractive options to advance carbohydrate vaccine development. However, limited knowledge on structure-property correlates hampers the discovery of immunoprotective carbohydrate epitopes. Recent advancements in tools for glycan modification, high-throughput screening of biological samples, and 3D structural analysis may facilitate antigen discovery process. This review focuses on advances that accelerate carbohydrate-based vaccine development and various technologies that are driving these efforts. Herein we provide a critical overview of approaches and resources available for rational design of better carbohydrate antigens. Structurally defined and fully synthetic oligosaccharides, designed based on molecular understanding of antigen-antibody interactions, offer a promising alternative for developing future carbohydrate vaccines.

Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine

“…In contrast, capsular polysaccharide vaccines and polysaccharide-or oligosaccharide-protein conjugate vaccines are in use for vaccination against several bacteria including S. pneumoniae, N. meningitides, Haemophilus influenzae type b (Hib) and S. typhi (16). However, current carbohydrate-based vaccines mostly provide protection for only a few serotypes, can lack efficacy in infants (although conjugate vaccines have partially overcome this problem), and none provide crossprotection against a wide range of bacterial species (10,16).…”

“…Of the various candidate antigens, bacterial carbohydrates (e.g., capsular polysaccharides and lipopolysaccharides) are often antigenic and humans can develop protective antibodies upon exposure by infection or vaccination (10). Due to wide antigenic variation of microbial carbohydrates, an immune response is often restricted to a particular species or subgroup (serotype) of bacteria (10).…”

“…Of the various candidate antigens, bacterial carbohydrates (e.g., capsular polysaccharides and lipopolysaccharides) are often antigenic and humans can develop protective antibodies upon exposure by infection or vaccination (10). Due to wide antigenic variation of microbial carbohydrates, an immune response is often restricted to a particular species or subgroup (serotype) of bacteria (10). This serotype specificity is reflected in the majority of carbohydrate-binding monoclonal antibodies (mAbs) with known structures where binding involves a particular carbohydrate epitope often located at the ends of polysaccharide chains (11).…”

Synthesis and immunological study of α-2,9-oligosialic acid conjugates as anti-group C meningitis vaccines

“…16 To overcome these limitations, conjugate vaccines made of synthetic carbohydrate antigens, which have defined structures, uncompromised purity and reproducibility, and free of bacterial contaminants, have received increasing attention. 17–19 Vaccines composed of synthetic oligosaccharides also offer the opportunity to decipher their detailed structure-immunogenicity relationships to guide rational design and further optimization of antigenic epitopes for vaccine development. 19 Consequently, we are interested in exploring anti-meningitis conjugate vaccines derived from synthetic oligosaccharide antigens.…”

Glycan Arrays: From Basic Biochemical Research to Bioanalytical and Biomedical Applications

“…Therefore, antiglycan antibodies are promising biomarkers, and glycan arrays are the ideal tools to detect antibodies to hundreds of glycans in high-throughput analysis (122). The second setting where antiglycan antibodies are major players are carbohydrate-based vaccines: In vaccine development, antibody levels and epitope specificity can be analyzed in both patients and vaccinated individuals (6,125). Biomarkers and vaccine targets often involve similar or identical carbohydrates.…”