Abstract
During the last decade there has been a growing interest in glycoimmunology, a relatively new research field dealing with the specific interactions of carbohydrates with the immune system. Pathogens’ cell surfaces are covered by a thick layer of oligo- and polysaccharides that are crucial virulence factors, as they mediate receptors binding on host cells for initial adhesion and organism invasion. Since in most cases these saccharide structures are uniquely exposed on the pathogen surface, they represent attractive targets for vaccine design. Polysaccharides isolated from cell walls of microorganisms and chemically conjugated to immunogenic proteins have been used as antigens for vaccine development for a range of infectious diseases. However, several challenges are associated with carbohydrate antigens purified from natural sources, such as their difficult characterization and heterogeneous composition. Consequently, glycoconjugates with chemically well-defined structures, that are able to confer highly reproducible biological properties and a better safety profile, are at the forefront of vaccine development. Following on from our previous review on the subject, in the present account we specifically focus on the most recent advances in the synthesis and preliminary immunological evaluation of next generation glycoconjugate vaccines designed to target bacterial and fungal infections that have been reported in the literature since 2011.
Highlights
Notwithstanding the great advances of modern medicine, infectious diseases still have a strong impact on public health, both in industrialized and developing countries, due to their significant health-related costs for clinical treatment
Following on from our previous review on the subject, in the present account we focus on the most recent advances in the synthesis and preliminary immunological evaluation of generation glycoconjugate vaccines designed to target bacterial and fungal infections that have been reported in the literature since 2011
The second-generation polysaccharide vaccines consist of native PS, produced and purified from natural sources and chemically conjugated to immunogenic carrier proteins able to elicit a T cell-dependent immune response
Summary
Notwithstanding the great advances of modern medicine, infectious diseases still have a strong impact on public health, both in industrialized and developing countries, due to their significant health-related costs for clinical treatment. A major drawback of polysaccharide-based vaccines, is their limited clinical efficacy They induce T cell-independent immune responses, featured by poor immunogenicity in children under 5 yMeoalercusleos f20a1g8,e2,3,ixnFeOlRdPeErElRyRaEnVdIEWimmunocompromised individuals, and fail to generate2coofn52ventional. The minimal sequences for recognition of all mIgGs were pentasaccharides AB(E)CD 16a and B(E)CDA 14a Following these encouraging results, some selected synthetic oligosaccharides were conjugated to tetanus toxoid (TT) protein and used for immunization studies in mice, leading to the identification of a hit glycoconjugate, 19b, containing the trimer of the pentasaccharide AB(E)CD. Mulard et al showed that anti-LPS IgG elicited by their synthetic TT conjugate 19b recognized SF2a bacteria and purified SF2a LPS [18] In addition to these promising findings, the influence of O-acetylation of S. flexneri 2a O-Ag fragments on antigenicity was studied by Mulard group [21]. These data couldn’t provide an exhaustive proof of the role of O-acetylation for S. flexneri 2a O-Ag and of the effect of multiple acetates on the antigen, this work showed that studies using synthetic oligosaccharides may contribute to a better understanding of the antigen-antibody molecular recognition event
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