Carriers and Antigens: New Developments in Glycoconjugate Vaccines

Abstract

Glycoconjugate vaccines have proven their worth in the protection and prevention of infectious diseases. The introduction of the Haemophilus influenzae type b vaccine is the prime example, followed by other glycoconjugate vaccines. Glycoconjugate vaccines consist of two components: the carrier protein and the carbohydrate antigen. Current carrier proteins are tetanus toxoid, diphtheria toxoid, CRM197, Haemophilus protein D and the outer membrane protein complex of serogroup B meningococcus. Carbohydrate antigens have been produced mainly by extraction and purification from the original host. However, current efforts show great advances in the development of synthetically produced oligosaccharides and bioconjugation. This review evaluates the advances of glycoconjugate vaccines in the last five years. We focus on developments regarding both new carriers and antigens. Innovative developments regarding carriers are outer membrane vesicles, glycoengineered proteins, new carrier proteins, virus-like particles, protein nanocages and peptides. With regard to conjugated antigens, we describe recent developments in the field of antimicrobial resistance (AMR) and ESKAPE pathogens.

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus

“…It has been stated that he presence of previous immunity to a carrier protein could possibly suppress the immune induction to the conjugate, owing to carrier-induced epitopic suppression (CIES) [ 19 , 20 ]. One of the clinical studies regarding this issue was on the meningococcal serogroup C conjugate (MCC) vaccine, which contains TT.…”

Klebsiella pneumoniae K2 capsular polysaccharide degradation by a bacteriophage depolymerase does not require trimer formation

“…As an alternative to antibiotic treatment, vaccines targeting bacterial CPS have demonstrated efficacy in combatting infections by pathogenic bacteria, including Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae ( 15 , 16 ). While whole CPS isolates from pathogenic bacteria induced relatively poor and T cell-independent immune responses ( 17 ), glycoconjugate vaccines created by conjugating CPS fragments to a carrier protein such as CRM197 were found to elicit stronger and long-lasting immune responses ( 18 – 20 ).…”

Site-Selective C–O Bond Editing of Unprotected Saccharides

“…Most of these bioactive molecules contain mono- or complex oligo-saccharide fragments, as seen in mithramycin and validamycin, and are obtained from fermentation or biomass. , Another subset of these compounds, such as empagliflozin and remdesivir, contains simpler monosaccharides or their analogs and is prepared through chemical synthesis. , At present, effective strategies for synthesis or modification of the class of complex saccharide-based molecules are barely available. , Even for the relatively simple monosaccharide-based molecules, the presence of multiple hydroxyl groups (and C–H bonds) with similar reactivities makes the development of concise synthesis and modification methods challenging. , One main effort of research in saccharide synthesis chemistry involves manipulating the anomeric position of sugars particularly for glycosylation reactions (Figure B). Examples of recent success include Jacobsen’s catalytic stereoselective glycosylation coupling of (minimally protected) sugars to prepare disaccharides. , Another major effort is dedicated to converting saccharides, especially inexpensive biomass-derived monosaccharides, into their derivatives such as “rare sugars” with biological functions. , Indeed, approximately ten percent of glycosylated bacterial metabolites fall under the category of nontypical carbohydrates that are not present on the human cell surface, making them excellent targets for drug discovery and carbohydrate-based vaccine development. − While the importance of rare sugars as essential pharmacophores has been demonstrated in these biological studies, synthetic challenges have limited the accessibility of these critical structures. Traditional synthetic strategies mainly rely on multiple-step synthesis (involving repetitive use of protection groups) from common monosaccharides or the implementation of the carefully designed de novo synthesis from simple feedstock chemicals. ,, In this context, the methodology for selectively editing common sugar skeletons directly to access diverse ranges of rare sugars is of the utmost importance and value.…”