Preclinical studies on new proteins as carrier for glycoconjugate vaccines

Abstract

Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197, the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae. Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides.

Meningococcal Vaccines: Current Status and Emerging Strategies

“…Protein D from non-typeable Haemophilus influenzae has been used in a multivalent pneumococcal vaccine. A recent study investigated 28 potential carrier proteins from different types of bacteria [ 50 ]. These proteins were conjugated to a model polysaccharide and of those, eight were selected as potential carriers for N. meningitidis .…”

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

“…This, in turn, has a profound influence on the ability of conjugate PBVs to redirect the humoral immune response away from carrier protein and toward hapten (115). Additionally, the number of MHC class II epitopes found within carrier protein primary sequence and their affinity for receptors can potentiate humoral immune response through (1) the targeting of specific human leukocyte antigen (HLA) haplotypes within a population and (2) the activation of helper T (T H ) cells (30,116). This applies more to the targeting of TCR, however, and as such will be discussed in future sections.…”

“…X-ray crystallography, genetic sequencing, epitope prediction algorithms, and in vivo studies of adjuvant properties have all lead to a better understanding of why some proteins are simply more immunogenic than others. Ultimately, differences in protein structure can result in different capacities for antigen to interact with cells and receptors that are key to triggering an immune response (30). Knowledge of this phenomenon has led to a situation where vaccines are no longer conceptualized based on whole antigen, but rather on immune receptor epitopes/ligands and propensity of an antigen (based on structural motifs) for uptake by antigen presenting cells (APCs).…”

Overview of β-Glucans from Laminaria spp.: Immunomodulation Properties and Applications on Biologic Models

“…As described above, β-glucan itself can exert broad anti-infective effects. Furthermore, LAM has also been shown to have protective effects against different microorganisms, such as bacterial infections [ 93 ], oral microbial species [ 94 ], Listeria monocytogenes [ 38 ], and Candida albicans [ 5 , 10 ]. β-glucan was also found to be recognized by neutrophil and polymorphonuclear leukocytes in response to C. albicans infection [ 95 ].…”

“…This mechanism that allows the recognition and responses to conserved structural components, particularly β-glucans, has evolved in mammals as a defense against fungal pathogens [ 10 ]. Research has shown that LAM with β-glucan from a non-fungal source may contribute to possible vaccination against different fungi ( Table 3 ), while more recently the use of proteins, derived from different bacteria, were conjugated to the polysaccharide LAM model and tested in mice for their ability to induce antibodies against the carbohydrate antigen [ 93 , 97 ].…”