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

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.

Oligosaccharide ligand tuning in design of third generation carbohydrate pneumococcal vaccines

Streptococcus pneumoniae can cause many types of dangerous infectious diseases such as otitis media, pneumonia, meningitis and others that are more common in the very young and very old age. Available to date commercial vaccines based on capsular polysaccharides of S. pneumoniae of clinically important strains (first generation carbohydrate vaccines) and conjugated vaccines based on these polysaccharides (second generation carbohydrate vaccines) have certain limitations in protective efficiency. However, the efficiency of vaccines can be increased by the use of third generation vaccines based on synthetic oligosaccharide ligands representing in their structures the protective epitopes of capsular polysaccharides. The proper choice of an optimal oligosaccharide ligand is the most important step in the design of third generation carbohydrate vaccines. Herein we overview our works on the synthesis of three oligosaccharides corresponding to one, “one and a half” and two repeating units of S. pneumoniae type 14 capsular polysaccharide, immunogenic conjugates thereof and comparative immunological study of their conjugates with bovine serum albumin, which was used as a model protein carrier. The ability of obtained products to raise antibodies specific to capsular polysaccharide and homologous oligosaccharides, the induction of phagocytosis by immune antisera and active protection of immunized animals from S. pneumoniae type 14 infection were evaluated. On the basis of the results obtained tetrasaccharide comprising the repeating unit of S. pneumoniae type 14 capsular polysaccharide is an optimal carbohydrate ligand to be used as a part of the third generation carbohydrate pneumococcal vaccine.

Improvement of the immune efficacy of carbohydrate vaccines by chemical modification on the GM3 antigen

N-modified GM3 glycoconjugates improved the efficiency of the vaccination without the combination of metabolic oligosaccharide engineering technology.

Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-β-Glucan IgG Responses in T Cell-Deficient Mice

ABSTRACTPolysaccharide-encapsulated fungi are the chief source of diseases in immunocompromised hosts such as those infected with human immunodeficiency virus or neutropenia patients. Currently available polysaccharide-protein conjugate vaccines are mainly T cell dependent and are usually ineffective in weakened immune systems. In this study, laminarin, a well-characterized β-1,3-glucan, was conjugated with a prokaryotically expressed recombinant fragment (amino acids [aa] 39 to 272) of calreticulin (rCRT/39–272), which exhibits extraordinarily potent immunogenicity and adjuvanticity in experimental animals. The resultant conjugate reserves the immunostimulatory effect of rCRT/39–272 on naïve murine B cells and is capable of eliciting anti-β-glucan IgG (mostly IgG1) responses in not only BALB/c mice but also athymic nude mice. Laminarin-CRT-induced mouse antibodies (Abs) are able to bind withCandida albicansand inhibit its growthin vitro. In addition, vaccination with laminarin-CRT partially protects mice from lethalC. albicanschallenge. These results imply that rCRT/39–272 could be used as an ideal carrier or adjuvant for carbohydrate vaccines aimed at inducing or boosting IgG responses to fungal infections in immunodeficient hosts.