Premium
Synthetic glycopeptide antigens for HIV vaccine design (469.1)
Author(s) -
Wang LaiXi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.469.1
Subject(s) - epitope , glycan , glycopeptide , glycosylation , hiv vaccine , glycoprotein , antigen , antibody , virology , biology , human immunodeficiency virus (hiv) , computational biology , chemistry , biochemistry , immunology , vaccine trial , antibiotics
Heavy glycosylation of the HIV‐1 outer envelope glycoprotein gp120 forms a dense glycan shield that constitutes a strong defense mechanism for viral immune evasion. Nevertheless, the recent discovery of a new class of glycan‐dependent broadly neutralizing antibodies (bNAbs) from HIV‐infected individuals, including PG9, PG16, PGT121, PGT128 and PGT135, suggests that the viral defensive carbohydrates can also serve as targets of vaccine. Epitope mapping indicates that these bNAbs target glycopeptide structures at the variable (V1V2 or V3) regions of gp120. However, further characterization of the fine epitopes is complicated by the glycosylation heterogeneity of gp120. We have launched a project aiming to characterize and reconstitute the minimal antigenic glycopeptide structures through synthetic chemistry. A series of homogeneous glycopeptides corresponding to the V1/V2 and V3 domains were synthesized by a chemoenzymatic method, in which defined N‐glycans were installed selectively at the conserved glycosylation sites (N156, N160, N301, and N332). This study permits a detailed assessment of the glycan specificity at the respective glycosylation sites for recognition by antibodies PG9, PG16, PGT121, and PGT128. The ability to reconstitute the minimal neutralizing epitopes using well‐defined synthetic glycopeptides provides a useful template for HIV vaccine design.