Toward a carbohydrate-based HIV-1 vaccine: synthesis and immunological studies of oligomannose-containing glycoconjugates.
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.
Institute of Human Virology, University of Maryland Biotechnology Institute, University of Maryland, Baltimore, Maryland 21201, USA.
Jiahong
J
Ni
Haijing
H
Song
Yadong
Y
Wang
Nicholas M
NM
Stamatos
Lai-Xi
LX
Wang
D016915:AIDS Vaccines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry*; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008358:Mannose / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011817:Rabbits
D016915:AIDS Vaccines; D006001:Glycoconjugates; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008358:Mannose