Rational design and immunogenicity of liposome-based diepitope constructs: application to synthetic oligosaccharides mimicking the Shigella flexneri 2a O-antigen.
Fiche publication
Date publication
août 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FRISCH Benoit
Tous les auteurs :
Said Hassane F, Phalipon A, Tanguy M, Guerreiro C, Belot F, Frisch B, Mulard LA, Schuber F
Lien Pubmed
Résumé
We have designed chemically defined diepitope constructs consisting of liposomes displaying at their surface synthetic oligosaccharides mimicking the O-antigen of the Shigella flexneri 2a lipopolysaccharide (B-cell epitope) and influenza hemagglutinin peptide HA 307-319 (Th epitope). Using well controlled and high-yielding covalent bioconjugation reactions, the two structurally independent epitopes were coupled to the lipopeptide Pam(3)CAG, i.e. a TLR2 ligand known for its adjuvant properties, anchored in preformed vesicles. The synthetic construct containing a pentadecasaccharide corresponding to three O-antigen repeating units triggered T-dependent anti-oligosaccharide and anti-S. flexneri 2a LPS antibody responses when administered i.m. to BALB/c mice. Moreover, the long-lasting anti-LPS antibody response afforded protection against a S. flexneri 2a challenge. These results show that liposome diepitope constructs could be attractive alternatives in the development of synthetic carbohydrate-based vaccines.
Référence
Vaccine. 2009 Aug 27;27(39):5419-26