Toward a Carbohydrate-Based HIV-1 Vaccine:Synthesis and Immunological Studies of Oligomannose-Containing Glycoconjugates

摘要

Human antibody 2G12 is a broadly neutralizing antibody that exerts its anti-HIV activity by targeting a novel oligomannose cluster on HIV-1 gp120.It was previously demonstrated that synthetic oligomannose clusters could mimic the carbohydrate epitope of 2G12 and showed enhanced antigenicity(Wang L.X.et al.(2004)Chem.Biol.11,127).This paper describes the synthesis of oligomannose-containing glycoconjugates that include either a carrier protein or a universal T-helper epitope peptide to provide an effective immunogen.It was shown that the synthetic neoglycoconjugates containing oligomannose clusters could be recognized by the human antibody 2G12.Rabbit immunization studies revealed that only a small fraction of antibodies raised by the glycoconjugates was directed to the carbohydrate antigens,with the majority of the IgG type antibodies being directed to the linkers in the conjugates.The anti-sera showed weak cross-reactivity to HIV-1 gp120.