Human immunodeficiency virus type-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV-1 envelope is a basic lipid bilayer that contains gp120 and gp41 glycoproteins. Several animal models studies have demonstrated that antibodies can provide considerable benefits against HIV or SIV (Simian Immunodeficiency Virus) challenge and prompted an inducing broadly neutralizing antibodies, an ultimate goal in HIV vaccine research. However, the HIV vaccine development has been deterred by the low antigenicity and immunogenicity of the HIV envelope glycoprotein gp120 and the efficient hiding of highly immunogenic epitopes by its glycans.        Recently, a new class of bNABs (PG9, PG16, PGT121-137 and PGT141-145) isolated from HIV positive donors, was shown to be potent in neutralizing primary HIV-1 strains across clades. Here we describe our efforts towards chemical and enzymatic synthesis of various gp-120 related high-mannose, hybrid and complex type N-Glycans. We studied specificities of various bNABs towards synthetic N-glycans printed on glass slides using carbohydrate microarray. Based on recognition patterns of bNABs to quaternary structure at variable domain (V1/V2 and V3 regions) of  gp-120, we created synthetic oligomannose constructs that more effectively mimic the glycan display found on gp120, and further optimized strategies to conjugate these constructs to carrier protein molecule

Design and synthesis of carbohydrate-based immunogens for eliciting broadly neutralizing antibodies to HIV

244th National Meeting (2012)

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