Design of a non-glycosylated outer domain-derived HIV-1 gp120 immunogen that binds to CD4 and induces neutralizing antibodies.

ABSTRACT: The outer domain (OD) of the HIV-1 envelope glycoprotein gp120 is an important target for vaccine design as it contains a number of conserved epitopes, including a large fraction of the CD4 binding site. Attempts to design OD-based immunogens in the past have met with little success. We report the design and characterization of an Escherichia coli-expressed OD-based immunogen (OD(EC)), based on the sequence of the HxBc2 strain. The OD(EC)-designed immunogen lacks the variable loops V1V2 and V3 and incorporates 11 designed mutations at the interface of the inner and the outer domains of gp120. Biophysical studies showed that OD(EC) is folded and protease-resistant, whereas OD(EC) lacking the designed mutations is highly aggregation-prone. In contrast to previously characterized OD construct

SUBMITTER: Bhattacharyya S 

PROVIDER: S-EPMC2930709 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature