Carrier priming with CRM197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: Biophysical and immunochemical interpretation

A Semi-synthetic Oligosaccharide Conjugate Vaccine Candidate Confers Protection against Streptococcus pneumoniae Serotype 3 Infection

“…Covalent attachment of carbohydrate antigens to carrier proteins produces neoglycoconjugates that, unlike native carbohydrates, induce a T cell-dependent immune response (Avery and Goebel, 1931; Pozsgay, 2000). Synthetic tetrasaccharide 1 was conjugated to the carrier protein CRM197, a widely used detoxified mutant of diphtheria toxin that is a constituent of licensed vaccines and induces little carrier-mediated suppression of anti-hapten responses (Tontini et al, 2013; Pecetta et al, 2015; Pecetta et al, 2016). Di-( N -succinimidyl) adipate (DSAP) was used as cross-linker.…”

Carrier priming effect of CRM 197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM 197 and diphtheria toxoid

“…The interference caused by circulating anti-carrier antibodies has also been recently described in humans: maternal antibodies elicited by a combined diphtheriatetanus-acellular pertussis-inactivated polio vaccine have been observed to interfere with the neonatal immune response to a following meningococcal C-CRM 197 conjugate immunization [50]. In our previous work, we compared the effect of a diphtheria-tetanus formulation on quadrivalent meningococcal CRM 197 or DT vaccines [26], and we may apply the approach here described to address similar complex priming immunizations.…”

“…We reported that, in the context of carrier priming experiments in mouse model, pre-exposure to CRM 197 induced a clear propensity to enhance the anti-carbohydrate response of the meningococcal CRM 197 conjugates; as opposed to DT, which induced CIES when used to prime meningococcal DT conjugates with a low carbohydrate:carrier ratio [25]. We found that the low intrinsic immunogenicity of CRM 197 as compared to DT, the conformational changes induced in CRM 197 by the chemical conjugation with MenA, and the cross-reactivity between anti-DT antibodies and DT glycoconjugates, might explain the different behavior of CRM 197 and DT in our carrier priming model [26].…”

“…Indeed, anti-carrier IgGs induced by DT priming had high titer and high avidity for DT based conjugates [26].…”

Preclinical studies on new proteins as carrier for glycoconjugate vaccines

“…Carrier priming and suppression effect were investigated in both animal and human studies and different behaviors between the commonly used carriers were reported [13][14][15]. Considering these aspects, novel carriers might help in avoiding or reducing the impact of the above mentioned issues and enable the further development of pediatric schedules and combinations [16].…”