Rational design and immunogenicity of liposome-based diepitope constructs: application to synthetic oligosaccharides mimicking the Shigella flexneri 2a O-antigen.
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.
Said Hassane
Fatouma
F
Université de Strasbourg, CNRS - UMR 7199, Faculté de Pharmacie, Illkirch, France.
Phalipon
Armelle
A
Tanguy
Myriam
M
Guerreiro
Catherine
C
Bélot
Frédéric
F
Frisch
Benoît
B
Mulard
Laurence A
LA
Schuber
Francis
F
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D004405:Dysentery, Bacillary / Q000276:immunology / Q000517:prevention & control; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006388:Hemagglutinins / Q000276:immunology; D055666:Lipopeptides / Q000737:chemistry / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D019081:O Antigens / Q000737:chemistry / Q000276:immunology*; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology*; D009975:Orthomyxoviridae; D012763:Shigella flexneri / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006388:Hemagglutinins; D055666:Lipopeptides; D008081:Liposomes; D019081:O Antigens; D009844:Oligosaccharides; D014614:Vaccines, Synthetic