Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments

Abstract

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.

Features and protective efficacy of human mAbs targeting Mycobacterium tuberculosis arabinomannan

“…Motifs within bacterial surface glycans serve as key targets for Ab-inducing glycoconjugate vaccines against several deadly human pathogens ( 49 , 50 ), but detailed knowledge about their role in M . tuberculosis infection is lacking.…”

“…While further studies with mAbs reacting with more defined and distinct AM epitopes will allow more granular investigations, these data suggest that reactivity with several specific capped and/or terminal/core Ara motifs promotes protective efficacy of anti-AM/LAM IgG. Given the successful development of semi- and fully synthetic carbohydrate vaccines that target specific glycan motifs and are now in preclinical and clinical studies ( 50 ), these data could have implications for TB vaccine development strategies.…”

“…Motifs within bacterial surface glycans serve as key targets for Ab-inducing glycoconjugate vaccines against several deadly human pathogens (49,50), but detailed knowledge about their role in M. tuberculosis infection is lacking. We have recently shown that polyclonal IgG from LTBI individuals against the M. tuberculosis surface glycan AM has protective in vitro and in vivo efficacy against M. tuberculosis and that reactivity to specific AM/ LAM OS motifs was associated with in vitro functions (14).…”

Development in the Concept of Bacterial Polysaccharide Repeating Unit-Based Antibacterial Conjugate Vaccines

“…As a result, this type of glycoconjugate vaccines is complex and batch-to-batch different. Another type of glycoconjugate vaccines has synthetic oligosaccharide antigens linked to CPs, which are called semi-synthetic conjugate vaccines (Figure b). − In these vaccines, the structure of carbohydrate antigens and their linkage forms to CPs are well defined, although the protein conjugation sites are usually undefined. The third type of glycoconjugate vaccines has synthetic carbohydrate antigens conjugated with synthetic carrier molecules, such as lipids, glycolipids, glycopeptides, oligosaccharides or polysaccharides and synthetic polymers, as well as other synthetic materials, which are called fully synthetic glycoconjugate vaccines (Figure c) .…”