Abstract
Currently licensed glycoconjugate vaccines are composed of a carbohydrate moiety covalently linked to a protein carrier. Polysaccharides are T-cell independent antigens able to directly stimulate B cells to produce antibodies. Disease burden caused by polysaccharide-encapsulated bacteria is highest in the first year of life, where plain polysaccharides are not generally immunogenic, limiting their use as vaccines. This limitation has been overcome by covalent coupling carbohydrate antigens to proteins that provide T cell epitopes. In addition to the protein carriers currently used in licensed glycoconjugate vaccines, there is a search for new protein carriers driven by several considerations: (i) concerns that pre-exposure or co-exposure to a given carrier can lead to immune interference and reduction of the anti-carbohydrate immune response; (ii) increasing interest to explore the dual role of proteins as carrier and protective antigen; and (iii) new ways to present carbohydrates antigens to the immune system. Protein carriers can be directly coupled to activated glycans or derivatized to introduce functional groups for subsequent conjugation. Proteins can be genetically modified to pre-determine the site of glycans attachment by insertion of unnatural amino acids bearing specific functional groups, or glycosylation consensus sequences for in vivo expression of the glycoconjugate. A large portion of the new protein carriers under investigation are recombinant ones, but more complex systems such as Outer Membrane Vesicles and other nanoparticles are being investigated. Selection criteria for new protein carriers are based on several aspects including safety, manufacturability, stability, reactivity toward conjugation, and preclinical evidence of immunogenicity of corresponding glycoconjugates. Characterization panels of protein carriers include tests before conjugation, after derivatization when applicable, and after conjugation. Glycoconjugate vaccines based on non-covalent association of carrier systems to carbohydrates are being investigated with promising results in animal models. The ability of these systems to convert T-independent carbohydrate antigens into T-dependent ones, in comparison to traditional glycoconjugates, needs to be assessed in humans.
Highlights
In the 1980s, glycoconjugate vaccines were introduced into the arsenal of available weapons for prevention of infectious diseases to overcome an important limitation of conventional polysaccharide (PS) vaccines [1]
While there are many reports on the preparation and characterization of glycoconjugate vaccines focusing on the glycan moiety, less attention has been put on aspects related to the protein carrier
Besides the proteins already established as carrier in licensed glycoconjugate vaccines, many other have been tested in preclinical studies and some in clinical trials; a notable example is the recombinant non-toxic form of Pseudomonas aeruginosa exotoxin A which has been used as carrier for Shigella O-antigens [28], Staphylococcus aureus type 5 and 8 capsular PS [29], and Salmonella Typhi Vi antigen [30,31], and is widely used for glycoconjugates directly synthesized in E. coli, known as bioconjugates [32,33,34,35]
Summary
In the 1980s, glycoconjugate vaccines were introduced into the arsenal of available weapons for prevention of infectious diseases to overcome an important limitation of conventional polysaccharide (PS) vaccines [1]. PS are defined as T-cell independent antigens which can directly stimulate B cells to produce antibodies They are made up of repetitive structures containing B cells but not T cell epitopes, the latter being essential to engage T cells and trigger a B-T cooperation, leading to a more complete immune response at any Molecules 2018, 23, 1451; doi:10.3390/molecules23061451 www.mdpi.com/journal/molecules. We provide an overview of the carriers for glycoconjugate vaccines, including traditional and more recently used recombinant proteins, exploited in some examples with the additional role of antigen. Novel carrier systems, such as inorganic nanoparticles, virus-like particles and Outer Membrane Vesicles (OMVs) are presented. Relevant aspects related to the impact of the carrier protein and the conjugation degree on the immune response of glycoconjugate vaccines, which need to be further investigated in humans, are here analyzed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
