Abstract
A new synthetic strategy for the development of multivalent antibacterial glycoconjugate vaccines is described. The approach comprises the utilization of an isocyanide-based multicomponent process for the conjugation of functionalized capsular polysaccharides of S. pneumoniae and S. Typhi to carrier proteins such as diphtheria and tetanus toxoids. For the first time, oxo- and carboxylic acid-functionalized polysaccharides could be either independently or simultaneously conjugated to immunogenic proteins by means of the Ugi-multicomponent reaction, thus leading to mono- or multivalent unimolecular glycoconjugates as vaccine candidates. Despite the high molecular weight of the two or three reacting biomolecules, the multicomponent bioconjugation proved highly efficient and reproducible. The Ugi-derived glycoconjugates showed notable antigenicity and elicited good titers of functional specific antibodies. To our knowledge, this is the only bioconjugation method that enables the incorporation of two different polysaccharidic antigens to a carrier protein in a single step. Applications in the field of self-adjuvanting, eventually anticancer, multicomponent vaccines are foreseeable.
Highlights
Multicomponent reactions (MCRs) are convergent processes in which three or more reactants are combined in one pot to render a product that incorporates atoms from all starting materials.[1]
This reaction has been seldom employed in the covalent modi cation of proteins, such as bovine serum albumin (BSA), horseradish peroxidase (HRP) and bovine pancreatic trypsin,[9] but not in such a way that several saccharidic components are simultaneously conjugated to a protein
The scope of this multicomponent bioconjugation is assessed by employing oxo- and carboxylic acid-functionalized capsular polysaccharides (CPs) of different bacteria or serotypes as well as tetanus toxoid (TT) and diphtheria toxoid (DT) as the amino components of the process, along with commercial isocyanides
Summary
Multicomponent polysaccharide–protein bioconjugation in the development of antibacterial glycoconjugate vaccine candidates†. Rodrıguez,b Dagmar Garcıa-Rivera, b Yury Valdes,b Vicente Verez-Bencomo*b and Daniel G. A new synthetic strategy for the development of multivalent antibacterial glycoconjugate vaccines is described. Oxo- and carboxylic acidfunctionalized polysaccharides could be either independently or simultaneously conjugated to immunogenic proteins by means of the Ugi-multicomponent reaction, leading to mono- or multivalent unimolecular glycoconjugates as vaccine candidates. The Ugi-derived glycoconjugates showed notable antigenicity and elicited good titers of functional specific antibodies. To our knowledge, this is the only bioconjugation method that enables the incorporation of two different polysaccharidic antigens to a carrier protein in a single step. Applications in the field of self-adjuvanting, eventually anticancer, multicomponent vaccines are foreseeable
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
