Sugar-Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines.
Angew Chem Int Ed Engl
; 54(45): 13198-203, 2015 Nov 02.
Article
en En
| MEDLINE
| ID: mdl-26350581
ABSTRACT
A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM197 protein carrier. In particular, two novel methods for site-selective glycan conjugation were developed to obtain conjugates with single attachment site on the protein, based on chemical modification of a disulfide bond and pH-controlled transglutaminase-catalyzed modification of lysine, respectively. Importantly, conjugation at the C186-201 bond resulted in significantly higher anti O-antigen bactericidal antibody titers than coupling to K37/39, and in comparable titers to conjugates bearing a larger number of saccharides. This study demonstrates that the conjugation site plays a role in determining the immunogenicity in mice and one single attachment point may be sufficient to induce high levels of bactericidal antibodies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Salmonella typhimurium
/
Glicoconjugados
/
Antígenos O
/
Vacunas contra la Salmonella
Límite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2015
Tipo del documento:
Article