Glycoconjugate vaccines: some observations on carrier and production methods

Abstract

Glycoconjugate vaccines use protein carriers to improve the immune response to polysaccharide antigens. The protein component allows the vaccine to interact with T cells, providing a stronger and longer-lasting immune response than a polysaccharide interacting with B cells alone. Whilst in theory the mere presence of a protein component in a vaccine should be sufficient to improve vaccine efficacy, the extent of improvement varies. In the present review, a comparison of the performances of vaccines developed with and without a protein carrier are presented. The usefulness of analytical tools for macromolecular integrity assays, in particular nuclear magnetic resonance, circular dichroism, analytical ultracentrifugation and SEC coupled to multi-angle light scattering (MALS) is indicated. Although we focus mainly on bacterial capsular polysaccharideprotein vaccines, some consideration is also given to research on experimental cancer vaccines using zwitterionic polysaccharides which, unusually for polysaccharides, are able to invoke T-cell responses and have been used in the development of potential all-polysaccharide-based cancer vaccines.A general trend of improved immunogenicity for glycoconjugate vaccines is described. Since the immunogenicity of a vaccine will also depend on carrier protein type and the way in which it has been linked to polysaccharide, the effects of different carrier proteins and production methods are also reviewed. We suggest that, in general, there is no single best carrier for use in glycoconjugate vaccines. This indicates that the choice of carrier protein is optimally made on a case-by-case basis, based on what generates the best immune response and can be produced safely in each individual case.

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

“…"lattice type") may be more challenging (Barel and Mulard 2019). Proven methods to measure molecular size distribution, hydrodynamic size, viscosity and solution behaviour (of the glycoconjugate or the separate polysaccharides and/or carrier proteins) include SEC-MALS/UV/RI/Viscosity, degree of polymerisation (repeating unit analysis), analytical ultracentrifugation and optical spectroscopy (MacCalman et al 2019).…”

“…Since capsular polysaccharides and serotype-specific Opolysaccharides are tightly linked with the virulence of enteric pathogenic bacteria, global efforts are being taken to develop vaccine candidates using these antigens to provide long-term antibody-mediated protection from enteric diseases (Cohen and Muhsen 2019). Low immunogenicity of many bacterial glycans can be compensated via carrier protein conjugation that helps to induce a T-cell-dependent response (Rappuoli et al 2018;Micoli et al 2018a, b, c;MacCalman et al 2019;Berti and Micoli 2020). Poor immunogenicity and heterogeneity of bacterial polysaccharides make glycoconjugate vaccine development a challenging but important task, as early successes show.…”

A Stable Nano-Vaccine for the Targeted Delivery of Tumor-Associated Glycopeptide Antigens

“…These studies were performed in two stages: First, we prepared B13Gs-AuNPs conjugated with the unglycosylated MUC4 peptide and immunized with two distinct adjuvants to determine the most efficient combination for immune enhancement; Second, the TF-Ser 5 glycopeptide was conjugated to B13Gs-AuNPs utilizing the adjuvant chosen in the first vaccination. In this step the glycopeptide was also conjugated to the a highly immune-stimulating protein carrier CRM197, a recombinant, non-toxic form of diptheria toxin used as a carrier protein for many polysaccharides 80–82 , as a “positive” control. This was done to compare the new platform to one known to elicit very powerful immune responses to many different haptens.…”

Glycan and Protein Analysis of Glycoengineered Bacterial E. coli Vaccines by MALDI-in-Source Decay FT-ICR Mass Spectrometry

“…Consequently, the comprehensive analytical characterization of glycoconjugate bacterial vaccines, needed to corroborate their structural integrity, is not trivial and requires a multi-methods approach. 27 …”