Recent Developments in Synthetic Oligosaccharide-Based Bacterial Vaccines

Abstract

Synthetic advances made possible chemical assembly of complex oligosaccharide fragments of polysaccharide domains on the surface of human pathogenic bacteria. These oligosaccharides may be recognized by antibodies raised against high molecular weight, native, polysaccharides. In addition to their antigenicity, synthetic oligosaccharides can also function as haptens in their protein conjugates that can elicit not only oligo- but also polysaccharide-specific IgG antibodies in animal models and in humans. A major milestone in the development of new generation vaccines was the demonstration that protein conjugates of synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b are as efficacious in preventing childhood meningitis and other diseases as is the corresponding licensed commercial vaccine containing the bacterial polysaccharide. The lessons learnt in this and other endeavors described herein are manifold. For example, they teach us about the significance of the oligosaccharide epitope size, the number of their copies per protein in the conjugate, the possible effect of the spacer on anti-saccharide immune response, and the proper choice of the carrier protein combined with the selection of the animal model. The H. influenzae b story also teaches us that that the synthetic approach can be commercially viable.

A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Shigella flexneri 2a Infection

“…The resulting licensing of Quimi Hib in Cuba in 2003 demonstrates the potential of the strategy in humans. However, despite an increasing number of encouraging reports, efficient third generation bacterial polysaccharide vaccines remain at an early stage of development (7,9,10). By demonstrating the induction of a protective anti-LPS Ab response against SF2a, using a conjugate incorporating a rationally designed synthetic OS mimic of LPS 2a, the current study provides an additional example of the potential of such an approach.…”

“…Despite this difficulty, vaccine candidates derived from LPS lacking full-length lipid A-chains are under investigation (2)(3)(4)(5)(6). Alternatively, progress in glycochemistry has opened the way to third generation polysaccharide vaccines, namely, synthetic carbohydrate-protein conjugate vaccines (7)(8)(9)(10).…”

Synthetic β-(1→6)-Linked N-Acetylated and Nonacetylated Oligoglucosamines Used To Produce Conjugate Vaccines for Bacterial Pathogens

“…Other synthetic oligosaccharide vaccines for a variety of pathogens are currently in various stages of development (32), indicating that more success with this technology is likely to come.…”

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines forShigella,Salmonella,enterotoxigenicE. coli(ETEC) enterohemorragicE. coli(EHEC) andCampylobacter jejuni

“…34 It has been proposed that, for several pathogens, the use of synthetic carbohydrates based on LPS structure may be promising in creating vaccine antigens (reviewed by Pozsgay). 35 Using a mouse model, researchers have tested synthetic carbohydrates, whose repeated units have been derived from the specific Shigella spp. LPS O-antigen.…”