Synthesis and Immunological Study of N-Glycan-Bacteriophage Qß Conjugates Reveal Dominant Antibody Responses to the Conserved Chitobiose Core.
Bioconjug Chem
; 33(7): 1350-1362, 2022 07 20.
Article
de En
| MEDLINE
| ID: mdl-35687881
ABSTRACT
N-Glycosylation plays an important role in many biological recognition processes. However, very few N-glycan-specific antibodies are available for functional studies and potentially for therapeutic development. In this study, we sought to synthesize bacteriophage Qß conjugates with representative N-glycans and investigate their immunogenicity for raising N-glycan-specific antibodies. An array of Qß glycoconjugates bearing five different human N-glycans and two different chemical linkers were synthesized, and the immunization of the N-glycan-Qß conjugates was performed in mice. We found that the N-glycan-Qß conjugates raised significant IgG antibodies that recognize N-glycans, but, surprisingly, most of the glycan-dependent antibodies were directed to the shared chitobiose core and were nonspecific for respective N-glycan structures. The linker chemistry was found to affect antibody specificity with adipic acid-linked N-glycan-Qß immunogens raising antibodies capable of recognizing both the N-acetylglucosamine (GlcNAc) moieties of the chitobiose core. In contrast, antibodies raised by N-glycan-Qß immunogens with a triazole linker preferentially recognized the innermost N-acetylglucosamine moiety at the reducing end. We also found that sialylation of the N-glycans significantly suppressed the immune response. Furthermore, the N-glycan-Qß immunogens with an adipic acid linker elicited higher glycan-specific antibody titers than the N-glycan-triazole-Qß immunogens. These findings delineate several challenges in eliciting mammalian N-glycan-specific antibodies through the conventional glycoconjugate vaccine design and immunization.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Acétyl-glucosamine
/
Production d'anticorps
Limites:
Animals
/
Humans
Langue:
En
Journal:
Bioconjug Chem
Sujet du journal:
BIOQUIMICA
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique